Dissertations / Theses: 'B cells'

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Jo, Tomoyasu. "LUBAC accelerates B-cell lymphomagenesis by conferring B cells resistance to genotoxic stress." Kyoto University, 2020. http://hdl.handle.net/2433/259010.

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Kobert, Antonia. "CNS-resident cells support MS-relevant B-cell responses." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=114274.

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The therapeutic success of peripheral B-cell depletion strategies in MS patients has identified B cells as important contributors to new relapsing disease activity in the periphery. However, they may also drive the CNS-compartmentalized inflammatory processes thought to underlie the chronic-progressive stages of disease. The long-term persistence of plasma cells in the CNS of MS patients, and cellular aggregates rich in B cells, T cells and FDC-like cells that have recently been identified in the meningeal compartment, suggest the inflamed MS CNS may be a B-cell fostering environment. The factors that contribute to such a permissive environment, however, have remained poorly understood.Here, we demonstrate that glial cells and their soluble products can support B-cell survival and MS-relevant B-cell responses, including co-stimulatory molecule expression and T-cell activation, effector-cytokine secretion and immunoglobulin production. Glial-cell derived factors have been shown to be abnormally elevated in CSF of MS patients, and we hypothesized that MS CSF may be able to support B-cell survival in-vitro. We demonstrate that CSF alone, in isolation of the complex cellular environment of the inflamed MS CNS, is not sufficient to support B-cell survival in culture. We then considered CNS-resident ECs as another source of B-cell support, and we demonstrate that soluble factors secreted by BBB and meningeal ECs can either enhance or regulate B-cell survival, and increase expression of the T-cell co-stimulatory molecule CD86.Our observations suggest that CNS-resident glial and endothelial cells and their soluble products may significantly contribute to a B-cell permissive environment and support MS-relevant B-cell effector functions within the inflamed MS CNS. L'appauvrissement des cellules B en périphérie est un traitement effectif chez les patients atteints de la SP et ce type cellulaire semblerait être un important médiateur lors des rechutes associés à la maladie. Toutefois, ils peuvent aussi induire les réactions inflammatoires compartimentées dans le SNC qui semblent être à la base des stades chroniques-progressifs de la maladie. La persistance des plasmocytes dans le SNC et les agrégations cellulaires riche en cellules B, cellules T et en cellules ressemblant aux CDFs dans les méninges des patients suggèrent que le SNC inflammé lors de la SP fonctionne comme étant un environnement favorisant les cellules B. Les facteurs qui contribuent à cet environnement permissif sont restés faiblement compris.Nous démontrons que les cellules gliales et leurs produits solubles peuvent supporter la survie des cellules B ainsi que les fonctions pertinentes à la SP, incluant l'expression des molécules co-stimulatrices et l'activation des cellules T, la sécrétion des cytokines effectrices et la production des immunoglobulines. Les produits solubles gliaux sont anormalement élevés dans la FCS des patients, nous avons donc supposé que le FCS de la SP pourrait supporter la survie des cellules B. Nous démontrons que le FCS seul, en isolement de l'environnement cellulaire complexe du SNC de la SP inflammé, n'est pas capable de supporter la survie des cellules B in-vitro. Nous démontrons aussi que les produits solubles sécrétés par les CEs de la BHE et des méninges peuvent augmenter ou modérer la survie des cellules B et peuvent aussi augmenter l'expression de la molécule co-stimulatrice CD86.Nos observations suggèrent que les cellules gliales et les CEs résidants dans le SNC ainsi que leur produits solubles peuvent significativement contribuer à un environnement permissif pour les cellules B et peuvent aussi supporter leurs fonctions effectrices pertinentes à la SP dans le SNC inflammé de patients.

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Bansal, Raj Rani. "B cell help provided by human γδ T cells". Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/36649/.

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Vγ9Vδ2 T cells are a minor subset of T cells in human blood that differ from all other lymphocytes by their specific responsiveness to (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), a metabolite produced by a large range of microbial pathogens. Vγ9Vδ2 T cells can be skewed towards distinct effector functions, in analogy to, and beyond, the emerging plasticity of CD4+ T cells. Depending on the microenvironment, Vγ9Vδ2 T cells can assume features reminiscent of Th1, Th2, Th17 and Treg cells as well as professional antigen presenting cells (APCs). The main focus of this PhD was to investigate the role of the follicular B helper T (Tfh) cell derived cytokine IL-21 in enhancing the ability of human Vγ9Vδ2 T cells in providing B cell help. In order to try to mimic the physiological conditions in the GC, an in vitro system of autologous Vγ9Vδ2 T cells and B cells from tonsils or blood, the microbial metabolite HMB-PP and IL-21 was used. HMB-PP induced up-regulation of IL-21 receptor on Vγ9Vδ2 T cells. In return, IL-21 played a co-stimulatory role in the expression of the B cell-attracting chemokine CXCL13, the CXCL13 receptor CXCR5, the co-stimulatory molecules inducible co-stimulator (ICOS), OX40 and CD70 by activated Vγ9Vδ2 T cells. IL-21 also enhanced the ability of activated Vγ9Vδ2 T cells to support antibody production by B cells. Furthermore, Vγ9Vδ2 T cells not only themselves became highly activated APC marker expressing cells but also modified activation and APC marker expression on B cells. Findings presented in this thesis provide evidence that IL-21 contributes to the acquisition of B cell helper functions by human Vγ9Vδ2 T cells. In secondary lymphoid tissues, the interaction between HMB-PP-responsive Vγ9Vδ2 T cells, IL-21-producing Tfh cells and B cells is likely to impact on the generation of high affinity, class-switched antibodies in microbial infections

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Crawford, Alison. "Role of B cells in influencing T cell responses." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/13483.

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Chen, Hui-Chen. "Role for cyclic adenosine monophosphate (cAMP) response element binding proteins in B lymphocyte development and functional maturation." Connect to this title online, 2003. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1061213266.

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Thesis (Ph. D.)--Ohio State University, 2003. Document formatted into pages. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2005 Aug. 19.

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Kavikondala, Sushma. "Dendritic cell and B cell interactions in systemic lupuserythematosus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39793710.

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Mühle, Kerstin. "Interaction of CD8+CD40L+ T cells with B cells." Doctoral thesis, Humboldt-Universität zu Berlin, 2018. http://dx.doi.org/10.18452/19127.

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ZTLs vermitteln die Eliminierung von infizierten und entarteten Zellen durch Apoptose. Neuste Erkenntnisse unserer Gruppe haben gezeigt, dass eine Subpopulation der CD8+ T-Zellen, anstelle der zytotoxischen Marker das Oberflächenmolekül CD40L exprimiert. Die Expression von CD40L ist bislang als Schlüsselmolekül für die CD4+ T-Zell vermittelte Hilfe bekannt, welche durch Bindung an den CD40 Rezeptor auf anderen Immunzellen induziert wird. Das von den CD4+ T–Zellen ausgehende CD40L Signal ist besonders für die T-Zell abhängige B-Zell Aktivierung und die Bildung von Keimzentren essentiell, in denen B-Zellen heranreifen und hochaffine Antikörper produzieren um den Organismus vor eindringenden Erregern zu schützen. Aufgrund der CD40L-assoziierten Helferfunktion sollte in dieser Arbeit untersucht werden, welche Auswirkungen die Interaktion von CD8+CD40L+ T-Zellen mit B Zellen hat. In in vitro Studien konnte gezeigt werden, dass 50% der antigen-spezifischen CD8+ T-Zellen nach Aktivierung durch B-Zellen CD40L hochregulieren. Sowohl auf RNA- als auch auf Proteinebene induzierten CD8+CD40L+ T-Zellen einen B-Zell Phänotyp, der stark dem von CD4+ T-Zellen stimulierten B-Zellen ähnelte. In Infektionsversuchen mit dem B-Zell-trophen Virus MHV-68 konnte gezeigt werden, dass transgene Mäuse mit CD40L defizienten CD8+ T-Zellen im Vergleich zu Kontrolltieren eine signifikante Reduktion der Keimzentrums-B-Zellen in den Lymphknoten der oberen Halsregion aufweisen. Eine genauere Betrachtung des B-Zell Repertoires von IgG Gedächtniszellen ergab jedoch, dass die Sequenzen der IGHJ3 Genfamilie bevorzugt für die Modifikation der CDR3 Region in Mäusen mit CD40L defizienten CD8+ T-Zellen verwendet wird, die eine entscheidende Rolle bei der Antigenerkennung spielt. Zusammengefasst kann mit dieser Arbeit zum ersten Mal gezeigt werden, dass CD8+CD40L+ T-Zellen Helferfunktionen durch Unterstützung der B-Zell Aktivierung und Bildung von Keimzentren übernehmen können. CTLs are important for the elimination of infected and degenerated cells by inducing apoptosis of the target cells. Recently our group identified a sub-population of CD8+ T cells expressing CD40L instead of common CTL markers. To that date, transient CD40L expression on T cells has been only described as a function of activated CD4+ T cells, which displays this key molecule for CD4+ T cell mediated help by binding to the CD40 receptor on other immune cells. Particularly, CD40L signaling provided by CD4+ T cells is indispensable for T cell dependent B cell activation and GC responses, which generate B cells secreting high affinity antibodies that protect the host from invading pathogens. Due to its associated helper functions, this thesis aimed to dissect whether CD40L positive CD8+ T cells are restricted to cytotoxic killing or if this sub-population possesses similar properties as CD4+ T cells when interacting with B cells. In vitro co-culture experiments showed that 50% of murine antigen specific CD8+ T cells up-regulated CD40L upon activation by antigen presenting B cells. When compared to CD40L deficient CD8+ T cells, the interaction of CD8+ CD40L+ T cells induced remarkable changes in B cells on the RNA and protein level and triggered a B cell phenotype resembling that of B cells primed by CD4+ T cells. By the infection of mice with the B cell trophic virus MHV-68, it was found that E8IcrexCD40Lflox transgenic mice lacking CD40L only on matured CD8+ T cells, exhibited a significant decrease of GC B cells in superficial cervical lymph nodes at the acute state of infection compared to WT mice. A closer look into the memory B cell repertoire revealed a preferred usage of the murine IGHJ3 gene family that modifies the CDR3 and thus the recognition groove of the B cell antibody in E8IcrexCD40Lflox mice. In summary, this work provides sufficient evidence that CD8+ CD40L+ T cells adopt helper-like functions by supporting B cell activation and subsequent GC formation.

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Lee, Michael Hweemoon. "Modulators of Dendritic Cells and B cells in Lupus." Diss., Temple University Libraries, 2019. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/565007.

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Microbiology and Immunology Ph.D. Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against ubiquitous self-antigens, many of which are nuclear autoantigens like dsDNA and chromatin (Pisetsky, 2016), and by elevated type I interferons (IFN) (Hooks et al., 1979; Weckerle et al., 2011), a family of pro-inflammatory cytokines that have antiviral activity (Pestka et al., 2004). Microarray analysis of peripheral blood mononuclear cells (PBMC) from SLE patients discovered the increased expression of IFN-responsive genes that was named the IFN Signature (Baechler et al., 2003a; Bennett et al., 2003b; Crow et al., 2003). Genome wide association studies indicate a clear genetic component in lupus pathogenesis (Chung et al., 2011; SLEGEN et al., 2008) and murine models of SLE confirm genetic drivers of the disease (Morel, 2010; Morel et al., 2000). However, the concordance of SLE in monozygotic twins is only 30-40% (Connolly and Hakonarson, 2012), while the inc Temple University--Theses

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Gao, Yuanyuan. "Studies on CD40 Signaling-Unpreventable B Cell Receptor-Mediated Apoptosis in T Cell-Dependent Bystander B Cells." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157848.

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Almond, Jason Baron. "Mechanisms of proteasome inhibitor-induced apoptosis of B-cell chronic lymphocytic leukaemia (B-CLL) cells." Thesis, University of Leicester, 2002. http://hdl.handle.net/2381/30761.

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Proteasome inhibitors, including lactacystin, LLnL (N-acetyl-N-leucinyl-L-leucinyl-L- norleucinal) and MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal), potently induce apoptosis in leukaemic B-cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL). This pro-apoptotic effect occurs in cells from patients at all stages of the disease, including those resistant to conventional chemotherapy, suggesting that proteasome inhibitors may be useful for treatment of B-CLL. Following initial inhibition of proteasomal activity and an increase in ubiquitinated proteins, these agents induce mitochondrial cytochrome c release and caspase-dependent apoptosis, involving cleavage/activation of caspases -2, -3, -7, -8 and - 9. Pre-treatment with the cell permeable caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe)fluoromethyl ketone (Z-VAD.fmk), does not prevent the release of cytochrome c or partial processing of caspase-9 but prevents activation of effector caspases and induction of apoptosis. These results suggest that the release of cytochrome c is caspase independent and that caspase-9 is the initiator caspase in proteasome inhibitor-induced apoptosis of B-CLL cells. Activation of B-CLL lysates with dATP results in the formation of an -700 kDa caspase-activating apoptosome complex containing Apaf-1. A similar complex is formed in B-CLL cells induced to undergo apoptosis by proteasome inhibitors. Mechanisms of proteasome inhibitor-induced apoptosis vary between cell types, but often involve accumulation of short-lived proteins such as p53, p27 and pro-apoptotic Bcl-2 family members, activation of the stress kinase JNK, or inhibition of NF-kB transcriptional activity. Proteasome inhibitor-induced apoptosis in B-CLL cells is not triggered by alterations in the Bcl-2:Bax ratio, increase in pro-apoptotic t-Bid, or alterations in p27, XIAP, cIAPl or cIAP2. There is also no accumulation of IkB proteins that would inhibit NFkB survival signalling. Although proteasome inhibitors cause an accumulation of p53 and p21, this is not sufficient to induce apoptosis, as etoposide causes more pronounced increases in these molecules but is a less potent inducer of apoptosis. Activation of the stress kinases c-Jun N- terminal kinase (JNK) and p38 also does not appear to be involved. Therefore proteasome inhibitors induce mitochondrial perturbation in B-CLL cells by an apparently novel mechanism.

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Aboalela, Ali Anwar. "Immune Reconstitution of B Cells Following Allogeneic Hematopoietic Cell Transplantation." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17331949.

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Objectives: Graft versus host disease (GVHD), infections and disease relapse continue to be major complications of allogeneic hematopoietic cell transplantation (HCT). B cell abnormalities have been associated with these complications, and the objective of these studies was to identify and quantify abnormalities of B cell recovery after allogeneic HCT. Methods: Flow cytometry was used to analyze peripheral blood from healthy donors (HD) and samples obtained at 1, 2, 3, 6, 9, 12, 18, 24, 30, and 36 months post HCT. A panel of 8 fluorophore-conjugated monoclonal antibodies specific for B cell surface markers was used to identify levels of total B cells, antigen naïve, antigen experienced, transitional B cells, naïve B cells, IgD memory, pre germinal, post germinal, and plasmablasts. Results: 224 male patients and 175 female patients (total N=399) with a median age of 58 years (range 19-74) were included in this study. 308 patients received reduced intensity and 91 received myeloablative conditioning for allogeneic HCT in the management of various hematological malignancies. The 2-year overall survival was 65% and progression free survival was 55%. The absolute number of total B cells in patients compared to HD remained low for 9 months (118.8 x 106/L vs 204 x 106/L, P < 0.02) and normal levels were reached by month 12. Recovering cells were primarily antigen naïve B cells and the frequency of antigen experienced B cells remained below normal when compared to HD for all time points post HCT (P < 0.0001). Within the antigen naïve compartment, the frequency of transitional B cells remained elevated and naïve B cells remained below normal until normal levels were reached by month 9. Within the antigen experienced compartment, the frequency of pre germinal cells was elevated compared to HD from 6 months (4.8% vs 0.70%; P < 0.0002) post HCT. Plasmablast frequencies were elevated compared to HD from 6 months (7.3% vs 1.1%; P < 0.0009) post HCT. IgD memory cells did not reach normal frequency for most time points. Post germinal cells did not reach normal frequencies from 6 to 12 months post HCT. Conclusion: Disturbances in B cell maturation after HCT persist for prolonged periods despite recovery of normal numbers of circulating B cells. Naïve and transitional B cells that predominate have low affinity BCRs and have been implicated in cGVHD. Reduced numbers of high affinity antigen experienced B cells likely predispose patients to infectious complications post HCT.

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Philips, Julia Rachel. "B-1 and B-2 B cell responses to lipopolysaccharide: Putative roles in the pathogenesis of periodontitis." Thesis, The University of Sydney, 2003. http://hdl.handle.net/2123/1852.

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Periodontal disease is one of the most widespread diseases in humans and is characterised by chronic gingival inflammation and B cell accumulation and resorption of the crest of alveolar bone with subsequent loss of teeth. Porphyromonas gingivalis has been identified as a putative aetiological agent for periodontitis. The aim of the research presented in this thesis was to investigate, using in vitro systems, the responses of autoreactive B-1 and B-2 cells to enterobacterial and nonenterobacterial lipopolysaccharide (LPS) to shed light on the pathogenesis of chronic periodontitis and other diseases involving B cell accumulation and autoantibody production. The hypotheses tested were: (1) B cells respond differently to enterobacterial and non-enterobacterial LPS. (2) B-1 cells are activated by a lower concentration of LPS than B-2 cells. (3) LPS stimulation results in preferential accumulation of B-1 cells. Findings consistent with these hypotheses would provide new evidence for different roles for B-1 and B-2 cells in immune responses and that LPS stimulation could lead to B-1 cell accumulation in diseases thus characterised. Initial experiments investigated the responses of representative B-1 (CH12) and B-2 (WEHI-279) cell lines to preparations of P. gingivalis and Salmonella enteritidis LPS utilising flow cytometric and quantitative molecular methods. The cell lines responded differently to the two LPS preparations. There were significant but limited effects on viability and proliferation in the WEHI-279 cell line, but no significant changes in mRNA expression levels for genes including Toll-like receptors (TLR2, TLR4, RP105), immunoglobulin (IgM), cytokines (IL-6, IL-10), co-stimulatory molecules (CD80, CD86), and regulators of apoptosis (Bcl-2, Bax). In the CH12 cell line however, LPS stimulation had greater effect. Addition of S. enteritidis LPS from a threshold level of 100ng/mL was found to rescue the cells from death, reflected by the percentage viability and proliferation. Stimulation of CH12 cells with S. enteritidis LPS also led to a decrease in expression of RP105 mRNA, which may be part of a negative feedback loop. Interestingly, stimulation with low concentrations P. gingivalis LPS appeared to inhibit proliferation but high LPS concentrations stimulated proliferation of CH12 cells, although no further significant effects were noted in other analyses. Evidence was found that CH12 cells have a high basal level of activation. This suggests that this line is constitutively activated. Stimulation with P. gingivalis or S. enteritidis LPS did not affect the level of CD80 mRNA expression. It is possible that the CH12 line constitutively expresses a maximal level of CD80 (and possibly CD86) and further stimulation will not cause any increase. Since S. enteritidis LPS appeared to have more pronounced effects on both B cell populations, this LPS was used to further investigate B cell subset responses in a mixed splenocyte culture system. Experiments examining percentage viability and number of viable cells indicated that B-1 and B-2 B cells responded differently to LPS stimulation. A threshold level for B-2 cell response (significant increase in cell number) was found to be 100ng/mL LPS, in contrast to the B-1 B cell subset which were only significantly different to the unstimulated cells when stimulated with 50μg/mL LPS. By examining the expression of CD80, the majority of murine splenic B-1 cells were found to activated prior to any LPS stimulation in vitro. In contrast, the B-2 subset showed significant increase in CD80 expression only at high (≥10μg/mL) LPS concentrations. Studies of the division index of B-1 and B-2 cells showed a significant response in both subsets following stimulation with 1μg/mL and 10μg/mL LPS. However, overall, the results are inconsistent with LPS driving the preferential accumulation of B-1 cells in disease states. These experiments provided useful evidence that supported the idea that B-1 and B-2 cells respond differently to LPS. However, these studies were unable to directly address the role of P. gingivalis LPS in periodontitis. It may be that P. gingivalis LPS could have different effects to S. enteritidis LPS on primary B cells. It is still possible that B-1 cells may be more sensitive to P. gingivalis, as opposed to S. enteritidis LPS. Studies by other groups have suggested that the TH1/TH2 profile is skewed towards TH2 in chronic periodontitis and that P. gingivalis may drive this shift via its ability to signal through TLR2 (and modulate TLR4 signalling). Further, recent studies in our laboratories have found that P. gingivalis gingipains are able to polyclonally activate B cells and to break down both IFNγ and IL-12. Future studies should further examine the effects of B-1 and B-2 interactions in the mixed lymphocyte system together with subsequent studies utilising human periodontitis biopsies. The results presented in this thesis, together with work undertaken by other investigators, suggests that LPS could perturb the normal homeostatic mechanisms of the B-1 B cell-subset and increase polyclonal activation therefore contributing to the genesis of pathologies such as chronic periodontitis.

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Kavikondala, Sushma. "Dendritic cell and B cell interactions in systemic lupus erythematosus." View the Table of Contents & Abstract, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39711523.

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Centuori, Sara M., Cecil J. Gomes, Samuel S. Kim, Charles W. Putnam, Brandon T. Larsen, Linda L. Garland, David W. Mount, and Jesse D. Martinez. "Double-negative (CD27−IgD−) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations." BIOMED CENTRAL LTD, 2018. http://hdl.handle.net/10150/627195.

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Background: The presence of B cells in early stage non-small cell lung cancer (NSCLC) is associated with longer survival, however, the role these cells play in the generation and maintenance of anti-tumor immunity is unclear. B cells differentiate into a variety of subsets with differing characteristics and functions. To date, there is limited information on the specific B cell subsets found within NSCLC. To better understand the composition of the B cell populations found in NSCLC we have begun characterizing B cells in lung tumors and have detected a population of B cells that are CD79A(+)CD27(-)IgD(-). These CD27(-)IgD(-)(double-negative) B cells have previously been characterized as unconventional memory B cells and have been detected in some autoimmune diseases and in the elderly population but have not been detected previously in tumor tissue. Methods: A total of 15 fresh untreated NSCLC tumors and 15 matched adjacent lung control tissues were dissociated and analyzed by intracellular flow cytometry to detect the B cell-related markers CD79A, CD27 and IgD. All CD79A(+) B cells subsets were classified as either naive (CD27(-)IgD(+)), affinity-matured (CD27(+)IgD(-)), early memory/germinal center cells (CD27(+)IgD(+)) or double-negative B cells (CD27(-)IgD(-)). Association of double-negative B cells with clinical data including gender, age, smoking status, tumor diagnosis and pathologic differentiation status were also examined using the logistic regression analysis for age and student's t-test for all other variables. Associations with other B cell subpopulations were examined using Spearman's rank correlation. Results: We observed that double-negative B cells were frequently abundant in lung tumors compared to normal adjacent controls (13 out of 15 cases), and in some cases made up a substantial proportion of the total B cell compartment. The presence of double-negative cells was also found to be inversely related to the presence of affinity-matured B cells within the tumor, Spearman's coefficient of -0.76. Conclusions: This study is the first to observe the presence of CD27(-)IgD(-)double-negative B cells in human NSCLC and that this population is inversely correlated with traditional affinity-matured B cell populations.

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Fichtner, Michael Verfasser], and Martin [Akademischer Betreuer] [Trepel. "Identification of B cell antigen receptor epitopes of mantle cell lymphoma B cells / Michael Fichtner ; Betreuer: Martin Trepel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://nbn-resolving.de/urn:nbn:de:gbv:18-81789.

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Fichtner, Michael [Verfasser], and Martin [Akademischer Betreuer] Trepel. "Identification of B cell antigen receptor epitopes of mantle cell lymphoma B cells / Michael Fichtner ; Betreuer: Martin Trepel." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2016. http://d-nb.info/1119319889/34.

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Lemoine, François Michel. "Studies of the interactions between stromal cells and B lymphoid progenitors." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/28856.

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The overall goal of the work, described in this thesis was to investigate the molecular mechanisms that regulate normal pre-B cell proliferation and how these may be altered in transformed pre-B cells. Monoclonal antibodies and molecular biological techniques have allowed a number of stages of pre-B cell differentiation to be defined but little is known about mechanisms controlling their proliferation. Studies of pre-B cell production in animal models and in long-term cultures that support pre-B cell proliferation have suggested that stromal cells play a key role in this regard. As a first step to investigate the mechanisms involved, a number of pre-B cell supportive murine stromal cell lines were isolated and characterized. A number of pre-B cell lines were also isolated, cloned and characterized. From these, spontaneous and Abelson murine leukemia virus transformants were derived. These cell lines were then used in co-culture experiments to demonstrate that stromal cells constitutively secrete a pre-B stimulating factor. Characterization of the pre-B cell stimulating activity produced by one stromal cell line (M2-10B4) showed it to be a 10 Kd molecule sensitive to freezing and different from any cloned hemopoietic growth factor described to date. The possibility that extracellular matrix components might be involved in stromal cell-mediated control of pre-B cell growth was also investigated. It was found that pre-B cells attach specifically to fibronectin and that although fibronectin by itself cannot support pre-B cell proliferation, it contributes to stromal cell stimulation of pre-B cell growth. Both of these mechanisms were found to be affected in malignantly transformed pre-B cell populations irrespective of the mode of transformation. Transformed pre-B cells were found to have acquired the ability to secrete a novel 3 Kd autocrine factor that is also capable of stimulating normal pre-B cells. In addition transformed pre-B cells showed a greatly decreased ability to adhere to fibronectin and had become insensitive to the synergistic stimulating effect of fibronectin. It will be of interest to determine in the future whether these findings have a counterpart in human malignant pre-B cell populations. Medicine, Faculty of Pathology and Laboratory Medicine, Department of Graduate

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Tun, Paul Fei-Tun. "BAFF, B cells and tumour immunity." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534210.

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O'Brien, Charlotte Rose. "B cells, Bach2 and immune deficiency." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/58936.

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B cell defects in HIV-1 infection are characterised by increased frequency of immature cell subsets, loss of memory cells, and hypergammaglobulinemia. There is increasing evidence that the capacity of B cells to secrete cytokines (IL-10) or express proteins (Bach2), may inhibit the T cell inflammatory response, which is believed to contribute to progressive immune deficiency in HIV-1. The aims were to determine if HIV-1 affects the capacity of B cells to express IL-10, TNF-α, and Bach2, and if alterations in cytokines and Bach2 expression were linked to T cell activation. An increase in immature B cell subsets and plasmablasts was found in HIV-1+ individuals, and was reversed by anti-retroviral therapy (ART). B cell proliferation and activation markers were increased in ART naïve individuals. However, TLR, T cell independent and dependent stimulation failed to increase expression of the co-stimulatory molecules, CD80 and CD86, or immunoglobulin synthesis, compared to healthy controls and HIV-1 patients on ART. No difference in the capacity of B cells to secrete IL-10 and TNF-α was noted in the study groups, and there was no association with markers of T cell activation. The results of flow cytometric Bach2 staining were unreliable. Analysis of B cell phenotype and function was undertaken in a patient with a history of chest infections and diarrhoea, and a heterozygous mutation in Bach2, c.T71C, was detected using whole exome sequencing. The patient did not have class-switched memory B cells, and decreased synthesis of immunoglobulins and cytokines. The immune findings supported the clinical phenotype of common variable immunodeficiency (CVID), which was confirmed by genetic correction experiments conducted by collaborators in the USA. In conclusion, HIV-1+ ART naïve patients retain the capacity to secrete cytokines despite a reduction in immunoglobulin synthesis. Mutation in Bach2 affects B cell maturation and function, and is implicated in the development of CVID.

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Lambert, David G. "Insulin release from cultured B-cells." Thesis, Aston University, 1987. http://publications.aston.ac.uk/14520/.

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Established RlNm5F and lN111 R1 and newly available HlT-T15 and UMR 407/3 B-cell lines have been successfully maintained in vitro. With the exclusion of UMR 407/3 cells, all lines were continuously propagable. Doubling times and plating efficiencies for HlT-T15, RlNm5F, lN111 R1 and UMR 407/3 cells were 20 hours and 85%, 31 hours and 76%, 24 hours and 80% and 38 hours and 94% respectively. All the cell lines were anchorage dependent, but only UMR 407/3 cells grew to confluence. Only HlT-T15 and UMR 407/3 cells produced a true insulin response to glucose but glucose markedly increased the rate of D-[U14C]glucose oxidation by all the cell lines. Glucose induced insulin release from HlT-T15 cells was biphasic with an exaggerated first phase. Insulin release from HlT-T15, RlNm5F and IN111 R1 cells was stimulated by amino acids and sulphonylureas. Glucagon stimulated insulin release from HlT-T15 and RlNm5F cells while somatostatin and pancreatic polypeptide inhibited release. These observations suggest that net insulin release from the whole islet may be the result of significant paracrine interaction. HlT-T15 and RlNm5F cell insulin release was stimulated by forskolin and inhibited by imidazole. Ca2+ channel blockade and calmodulin inhibition suppressed insulin release from HlT-T15, RlNm5F and IN111 R1 cells. In addition phorbol esters stimulated insulin release from RlNm5F cells. These data implicate cAMP, Ca2+ and protein kinase-C in the regulation of insulin release from cultured B-cells. Acetylcholine increased insulin release from HlT-T15 and RlNm5F cells. Inhibition of the response by atropine confirmed the involvement of muscarinic receptors. HlT-T15 cell insulin release was also inhibited by adrenaline. These observations suggest a possible role for the autonomic nervous system in the modulation of insulin release. Preliminary studies with a human insulinoma maintained in monolayer culture have demonstrated a limited life span of some seven weeks, a continuous low level of insulin release but no insulin response to glucose challenge.

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Liu, Jing. "Regulation of VH replacement in human immature B cells by B cell receptor (BCR)-mediated signaling." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2009. https://www.mhsl.uab.edu/dt/2010p/liu.pdf.

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28

Blink, Elizabeth J. "B cell selection in the germinal centre /." Connect to thesis, 2002. http://eprints.unimelb.edu.au/archive/00001459.

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29

Mosti, Laura [Verfasser], and Anton [Akademischer Betreuer] Cathomen. "Generation of safe CAR T cells to target B cell malignancies." Freiburg : Universität, 2021. http://d-nb.info/1232174378/34.

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30

Philips, Julia Rachel. "B-1 And B-2 B Cell Responses To Lipopolysaccharide: Putative Roles In The Pathogenesis Of Periodontitis." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/4395.

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Master of Science Periodontal disease is one of the most widespread diseases in humans and is characterised by chronic gingival inflammation and B cell accumulation and resorption of the crest of alveolar bone with subsequent loss of teeth. Porphyromonas gingivalis has been identified as a putative aetiological agent for periodontitis. The aim of the research presented in this thesis was to investigate, using in vitro systems, the responses of autoreactive B-1 and B-2 cells to enterobacterial and nonenterobacterial lipopolysaccharide (LPS) to shed light on the pathogenesis of chronic periodontitis and other diseases involving B cell accumulation and autoantibody production. The hypotheses tested were: (1) B cells respond differently to enterobacterial and non-enterobacterial LPS. (2) B-1 cells are activated by a lower concentration of LPS than B-2 cells. (3) LPS stimulation results in preferential accumulation of B-1 cells. Findings consistent with these hypotheses would provide new evidence for different roles for B-1 and B-2 cells in immune responses and that LPS stimulation could lead to B-1 cell accumulation in diseases thus characterised. Initial experiments investigated the responses of representative B-1 (CH12) and B-2 (WEHI-279) cell lines to preparations of P. gingivalis and Salmonella enteritidis LPS utilising flow cytometric and quantitative molecular methods. The cell lines responded differently to the two LPS preparations. There were significant but limited effects on viability and proliferation in the WEHI-279 cell line, but no significant changes in mRNA expression levels for genes including Toll-like receptors (TLR2, TLR4, RP105), immunoglobulin (IgM), cytokines (IL-6, IL-10), co-stimulatory molecules (CD80, CD86), and regulators of apoptosis (Bcl-2, Bax). In the CH12 cell line however, LPS stimulation had greater effect. Addition of S. enteritidis LPS from a threshold level of 100ng/mL was found to rescue the cells from death, reflected by the percentage viability and proliferation. Stimulation of CH12 cells with S. enteritidis LPS also led to a decrease in expression of RP105 mRNA, which may be part of a negative feedback loop. Interestingly, stimulation with low concentrations P. gingivalis LPS appeared to inhibit proliferation but high LPS concentrations stimulated proliferation of CH12 cells, although no further significant effects were noted in other analyses. Evidence was found that CH12 cells have a high basal level of activation. This suggests that this line is constitutively activated. Stimulation with P. gingivalis or S. enteritidis LPS did not affect the level of CD80 mRNA expression. It is possible that the CH12 line constitutively expresses a maximal level of CD80 (and possibly CD86) and further stimulation will not cause any increase. Since S. enteritidis LPS appeared to have more pronounced effects on both B cell populations, this LPS was used to further investigate B cell subset responses in a mixed splenocyte culture system. Experiments examining percentage viability and number of viable cells indicated that B-1 and B-2 B cells responded differently to LPS stimulation. A threshold level for B-2 cell response (significant increase in cell number) was found to be 100ng/mL LPS, in contrast to the B-1 B cell subset which were only significantly different to the unstimulated cells when stimulated with 50μg/mL LPS. By examining the expression of CD80, the majority of murine splenic B-1 cells were found to activated prior to any LPS stimulation in vitro. In contrast, the B-2 subset showed significant increase in CD80 expression only at high (≥10μg/mL) LPS concentrations. Studies of the division index of B-1 and B-2 cells showed a significant response in both subsets following stimulation with 1μg/mL and 10μg/mL LPS. However, overall, the results are inconsistent with LPS driving the preferential accumulation of B-1 cells in disease states. These experiments provided useful evidence that supported the idea that B-1 and B-2 cells respond differently to LPS. However, these studies were unable to directly address the role of P. gingivalis LPS in periodontitis. It may be that P. gingivalis LPS could have different effects to S. enteritidis LPS on primary B cells. It is still possible that B-1 cells may be more sensitive to P. gingivalis, as opposed to S. enteritidis LPS. Studies by other groups have suggested that the TH1/TH2 profile is skewed towards TH2 in chronic periodontitis and that P. gingivalis may drive this shift via its ability to signal through TLR2 (and modulate TLR4 signalling). Further, recent studies in our laboratories have found that P. gingivalis gingipains are able to polyclonally activate B cells and to break down both IFNγ and IL-12. Future studies should further examine the effects of B-1 and B-2 interactions in the mixed lymphocyte system together with subsequent studies utilising human periodontitis biopsies. The results presented in this thesis, together with work undertaken by other investigators, suggests that LPS could perturb the normal homeostatic mechanisms of the B-1 B cell-subset and increase polyclonal activation therefore contributing to the genesis of pathologies such as chronic periodontitis.

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31

Philips, Julia Rachel. "B-1 and B-2 B cell responses to lipopolysaccharide putative roles in the pathogenesis of periodontitis /." University of Sydney, 2006. http://hdl.handle.net/2123/1852.

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Master of Science Periodontal disease is one of the most widespread diseases in humans and is characterised by chronic gingival inflammation and B cell accumulation and resorption of the crest of alveolar bone with subsequent loss of teeth. Porphyromonas gingivalis has been identified as a putative aetiological agent for periodontitis. The aim of the research presented in this thesis was to investigate, using in vitro systems, the responses of autoreactive B-1 and B-2 cells to enterobacterial and nonenterobacterial lipopolysaccharide (LPS) to shed light on the pathogenesis of chronic periodontitis and other diseases involving B cell accumulation and autoantibody production. The hypotheses tested were: (1) B cells respond differently to enterobacterial and non-enterobacterial LPS. (2) B-1 cells are activated by a lower concentration of LPS than B-2 cells. (3) LPS stimulation results in preferential accumulation of B-1 cells. Findings consistent with these hypotheses would provide new evidence for different roles for B-1 and B-2 cells in immune responses and that LPS stimulation could lead to B-1 cell accumulation in diseases thus characterised. Initial experiments investigated the responses of representative B-1 (CH12) and B-2 (WEHI-279) cell lines to preparations of P. gingivalis and Salmonella enteritidis LPS utilising flow cytometric and quantitative molecular methods. The cell lines responded differently to the two LPS preparations. There were significant but limited effects on viability and proliferation in the WEHI-279 cell line, but no significant changes in mRNA expression levels for genes including Toll-like receptors (TLR2, TLR4, RP105), immunoglobulin (IgM), cytokines (IL-6, IL-10), co-stimulatory molecules (CD80, CD86), and regulators of apoptosis (Bcl-2, Bax). In the CH12 cell line however, LPS stimulation had greater effect. Addition of S. enteritidis LPS from a threshold level of 100ng/mL was found to rescue the cells from death, reflected by the percentage viability and proliferation. Stimulation of CH12 cells with S. enteritidis LPS also led to a decrease in expression of RP105 mRNA, which may be part of a negative feedback loop. Interestingly, stimulation with low concentrations P. gingivalis LPS appeared to inhibit proliferation but high LPS concentrations stimulated proliferation of CH12 cells, although no further significant effects were noted in other analyses. Evidence was found that CH12 cells have a high basal level of activation. This suggests that this line is constitutively activated. Stimulation with P. gingivalis or S. enteritidis LPS did not affect the level of CD80 mRNA expression. It is possible that the CH12 line constitutively expresses a maximal level of CD80 (and possibly CD86) and further stimulation will not cause any increase. Since S. enteritidis LPS appeared to have more pronounced effects on both B cell populations, this LPS was used to further investigate B cell subset responses in a mixed splenocyte culture system. Experiments examining percentage viability and number of viable cells indicated that B-1 and B-2 B cells responded differently to LPS stimulation. A threshold level for B-2 cell response (significant increase in cell number) was found to be 100ng/mL LPS, in contrast to the B-1 B cell subset which were only significantly different to the unstimulated cells when stimulated with 50μg/mL LPS. By examining the expression of CD80, the majority of murine splenic B-1 cells were found to activated prior to any LPS stimulation in vitro. In contrast, the B-2 subset showed significant increase in CD80 expression only at high (≥10μg/mL) LPS concentrations. Studies of the division index of B-1 and B-2 cells showed a significant response in both subsets following stimulation with 1μg/mL and 10μg/mL LPS. However, overall, the results are inconsistent with LPS driving the preferential accumulation of B-1 cells in disease states. These experiments provided useful evidence that supported the idea that B-1 and B-2 cells respond differently to LPS. However, these studies were unable to directly address the role of P. gingivalis LPS in periodontitis. It may be that P. gingivalis LPS could have different effects to S. enteritidis LPS on primary B cells. It is still possible that B-1 cells may be more sensitive to P. gingivalis, as opposed to S. enteritidis LPS. Studies by other groups have suggested that the TH1/TH2 profile is skewed towards TH2 in chronic periodontitis and that P. gingivalis may drive this shift via its ability to signal through TLR2 (and modulate TLR4 signalling). Further, recent studies in our laboratories have found that P. gingivalis gingipains are able to polyclonally activate B cells and to break down both IFNγ and IL-12. Future studies should further examine the effects of B-1 and B-2 interactions in the mixed lymphocyte system together with subsequent studies utilising human periodontitis biopsies. The results presented in this thesis, together with work undertaken by other investigators, suggests that LPS could perturb the normal homeostatic mechanisms of the B-1 B cell-subset and increase polyclonal activation therefore contributing to the genesis of pathologies such as chronic periodontitis.

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32

Feldhahn, Niklas. "Mimicry of a constitutively active pre-B cell receptor in BCR-ABL1-transformed pre-B leukemia cells." [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=979851769.

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33

Le, Thuc-vy L. "B cell clonal abundance and madcam-1 mediate affinity maturation and fate of germinal center B cells." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/le.pdf.

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34

Otero, Dennis C. "CD19 affects B-cell lymphopoiesis at multiple stages influencing survival, proliferation and differentiation of developing B-cells /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p3022214.

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35

Chan, Kwok-hung, and 陳國雄. "Epstein-Barr virus mediated B lymphocyte transformation and B cell ontogeny." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1994. http://hub.hku.hk/bib/B31234100.

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36

Chan, Kwok-hung. "Epstein-Barr virus mediated B lymphocyte transformation and B cell ontogeny /." Hong Kong : University of Hong Kong, 1994. http://sunzi.lib.hku.hk/hkuto/record.jsp?B17391143.

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37

Bashford-Rogers, Rachael Jennifer Mary. "Analysing the B-cell repertoire : investigating B-cell population dynamics in health and disease." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708880.

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38

Zao, Chih-Ling. "B Virus Circumvents Innate Responses in Human Cells." Digital Archive @ GSU, 2008. http://digitalarchive.gsu.edu/biology_diss/41.

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B virus (Cercopithecine herpesvirus 1) is an alphaherpesvirus indigenous to macaque monkeys and is closely related to herpes simplex virus type 1 (HSV-1). Disease caused by B virus, which is often mild or asymptomatic in its natural host, the macaque monkey, is similar in infected macaques to HSV-1 infection in humans. When B virus zoonotically infects foreign hosts, e.g., humans, high morbidity and mortality are evidenced in > 80% of untreated cases. To explore the underlying reasons for differences in pathogenesis between B virus and HSV-1 infection in humans, human microarrays were used to comparatively examine global cellular gene expression patterns engaged as a result of infection of human foreskin fibroblasts (HFFs). Our results demonstrate that these closely related simplexvirus family members have divergent strategies to thwart host cell pathways related to innate defenses. In these studies, B virus did not induce detectable interferon, cytokine or chemokine genes, in sharp contrast to HSV-1, which induced innate immune responsive genes in infected cells. Although no innate immune response genes were found to be up-regulated by B virus infection, B virus induced I£eB£a, which was the only gene found to be involved in the NF-£eB signaling pathway within the innate immunity biological network. Quantification of NF-£eB p50 DNA binding activity in virus-infected nuclear extracts demonstrated that NF-£eB p50 DNA binding activity was lower in B virus-infected cells. Suppression of I£eB£a in B virus infected cells by siRNA restored NF-£eB-induced cytokine and chemokine expressions. Data presented here support the model that I£eB£a inhibits NF-£eB regulated immune responsive genes in B virus-infected HFF cells, and this response differs from that observed in HFF cells infected with HSV-1. The result is that B virus alters the NF-£eB regulated expression of cytokine and chemokine genes of HFF cells differently from HSV-1 early after infection. These differences in cytokine and chemokine expression may be associated with the delayed or reduced host responses observed in B virus infected humans and underlie the failure of adaptive responses in zoonotically infected humans.

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39

Hartweger, H. "The function of Themis2 in B cells." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1460492/.

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Thymocyte-expressed molecule involved in selection 2 (Themis2) is the second member of the Themis family. Recently, the first member of the Themis family, Themis, has been reported to be part of the TCR signalling cascade and its deletion severely affects thymocyte progression from the double positive to the single positive stage. All family members share similar domains and high sequence similarity and show tissue specific expression with Themis2 being expressed in B lymphocytes, macrophages and dendritic cells. THEMIS2 associates with BCR signalling molecules such as GRB2, VAV or LYN and is phosphorylated in response to BCR stimulation. For these reasons I hypothesised that Themis2 might have an important role in B cell development or activation. I show that Themis2 is expressed throughout the B cell lineage and exclude redundant expression of other Themis family members. After B cell activation Themis2 expression is downregulated. Analysis of a newly created Themis2-deficient mouse strain showed that B cell development proceeds normally in the absence of THEMIS2. Experiments on in vitro cultured Themis2-deficient primary B cells demonstrated that proliferation and survival, BCR internalisation and antigen presentation as well as expression of activation markers and cytokines were unaffected. RNA sequencing revealed only minor changes in transcription in follicular B cells, even after activation. Similarly, antibody levels to in vivo immunisation with T-dependent or T-independent antigens or challenge with influenza virus did not suggest that Themis2 is required for antibody responses either. Reactions to a model of acute allergic airway inflammation showed only marginally reduced cell numbers in the bronchoalveolar lavage fluid yet all other markers of inflammation were all normal. In conclusion, I found that Themis2 is not required for B cell development, activation or antibody responses. Further studies will be required to define the role of Themis2 in the immune system.

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40

Oliver-Bell, Jessica. "The role of B cells in periodontitis." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/6464/.

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Introduction: Varying degrees of periodontal disease affect the majority of the population. Severe forms of periodontitis have a considerable impact on oral health and quality of life. Periodontitis results from imbalances in the oral microbiome and the host immune response. The mainstay of periodontal treatment – removal of dental plaque – is only partially successful. B cells infiltrate the gingiva of periodontitis patients, but their role in pathology has not been well characterised. The overarching aim of this research was to better characterise the role of B cells in periodontitis. Periodontitis shares similarities in risk factors and aspects of immunopathology with rheumatoid arthritis. Epidemiological evidence suggests patients with rheumatoid arthritis are more likely to have periodontitis, which cannot be completely explained by shared risk factors. This has led to the hypothesis that the two diseases are immunologically linked, and that periodontitis may precede, and cause, rheumatoid arthritis. A further objective of this research was to investigate whether the autoimmunity characteristic of rheumatoid arthritis emerges in periodontitis. Results: B cell infiltrate in the gingiva of periodontitis patients was confirmed. Periodontitis patients were found to have elevated serum titers of anti-citrullinated peptide antibodies which were generally below the diagnostic threshold for rheumatoid arthritis, and were reduced following non-surgical periodontal treatment. In a murine model of periodontitis, subtle changes to B cell phenotype were observed in tissues regional to the oral cavity in mice with periodontitis, at an early stage of disease. Such changes included increased B cell expression of receptor activator of NfκB ligand in the gingiva, and increased proportions of GC B cells in the draining lymph nodes. Some of these trends were enhanced in mice with periodontitis exacerbated by interleukin-33 treatment. B cell-deficient mice were protected from the alveolar bone loss normally induced in the model of periodontitis. Conclusion: B cells form a substantial proportion of the inflammatory infiltrate in the gingiva of periodontitis patients. Treatment of periodontitis can reduce titers of anti-citrullinated peptide antibodies in patients, potentially reducing their risk of developing rheumatoid arthritis. Evidence from B cell-deficient mice suggests that B cells contribute to pathological alveolar bone loss. Therefore, B cells may be worthy of targeting therapeutically in periodontitis.

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Kumari, Anita. "Mechanics of antigen extraction by B cells." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCB037/document.

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Les lymphocytes B sont un des éléments essentiels de l’immunité adaptative de par leur fonction de production d’anticorps. In vivo, leur activation est principalement déclenchée par l’engagement de leur récepteur BCR (B cell receptor) associé à des antigènes présents à la surface des cellules voisines. Cette interaction conduit à la formation d'une synapse immunitaire qui coordonne les événements de réorganisation de la signalisation et du cytosquelette qui sont essentiels pour l’extraction et le traitement des antigènes par les lymphocytes B. Deux modèles ont été proposés pour l'extraction d’antigènes : (1) L'étalement des membranes suivie d'une contraction cellulaire et (2) l'extraction mécanique directe des complexes moléculaires BCR-antigène. Selon le premier modèle, la reconnaissance spécifique par le BCR des antigènes liés à la bicouche lipidique, conduit à la contraction du cytosquelette d'actine transportant les antigènes associés au BCR vers le centre de la synapse. Le deuxième modèle résulte d'observations effectuées à l'aide d'un microscope à force atomique, d'antigènes associés à la membrane plasmatique suggérant que la protéine motrice myosine II tire activement sur des complexes BCR-antigène dans des puits enduits de clathrine. Il a également été montré que les antigènes peuvent être internalisés via la sécrétion de protéase à la synapse, mais cette voie ne s'active que si la voie mécanique échoue, typiquement sur des substrats non déformables enduits d'antigènes. Dans cette étude, nous avons développé une méthode pour extraire des modèles de force en utilisant des substrats déformables enduits d'antigènes pour la visualisation directe de la force (microscopie de force de traction, TFM). Nous démontrons l'existence de forces contractiles globales à la périphérie de la synapse et des forces d'attraction locales au centre. Les forces contractiles périphériques dépendent de l'organisation centripète de la myosine II, alors que les forces de traction centrales sont générées par des protubérances de F-actine formées de manière dépendante à la myosine II. Nous avons observé des contractions pulsatives et collectives, qui mettent potentiellement en évidence l'organisation de structures d'actine au centre de la synapse par l'intermédiaire de l'activité de la myosine II par intermittence. Nos résultats proposent donc un modèle unifié pour l'extraction de l'antigène par les lymphocytes B, où la myosine II est nécessaire pour la contraction cellulaire globale ainsi que pour l'internalisation de l'antigène par la régulation locale de la dynamique de l'actine. Il est important de noter que les méthodes et le modèle proposés ici peuvent être généralisés à d'autres systèmes impliquant l’association de molécules associé à une surface pouvant concerner de nombreux processus d’endocytose in vivo B cells produce antibodies and are therefore essential effectors of adaptive immunity. In vivo, their activation is mostly triggered by the engagement of their B cell receptor (BCR) with antigens exposed at the surface of neighboring antigen presenting cells. This leads to formation of an immune synapse that coordinates the signaling and cytoskeleton rearrangement events that are essential for B cells to extract and process antigens. Two models have been proposed for extraction of surface-tethered antigens by B cells: (1) Membrane spreading followed by cell contraction and (2) direct mechanical pulling on BCR-antigen molecular complexes. According to the first model, specific recognition by the BCR of antigens bound to supported lipid bilayer leads to contraction of the actin cytoskeleton, transporting BCR-bound antigens towards the centre of the synapse. The second model arose from observations made using atomic force microscopy of antigens tethered to plasma membrane sheets, which suggest the actin based motor protein myosin II actively pulls on BCR-antigen complexes in clathrin coated pits. It has also been shown that antigens can be internalized via protease secretion at the synapse, but this pathway only activate if the mechanical pathway fails, typically on non-deformable antigen coated substrates. In this study, we developed a method for extracting force patterns using antigen-coated substrate deformations for direct force visualization (traction force microscopy, TFM). We demonstrate the existence of global contractile forces at the periphery of the synapse and local pulling forces at its center. Peripheral contractile forces were dependent on the centripetal organization of myosin II, whereas central pulling forces were generated by F-actin protrusions formed in a myosin II-dependent manner. We observed collective pulsatile contractions, potentially underlying the organization of actin structures in the center of the synapse through intermittent myosin II activity. Our results thus propose a unified model for antigen extraction by B cells where myosin II is needed for global cell contractility as well as for antigen internalization through local regulation of actin dynamics. Importantly, the methods and model proposed here may be generalizable to other systems involving surface-tethered molecules, as this model might concern many endocytic processes in vivo

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Berti, Alvise. "Autoreactive B Cells in ANCA-Associated Vasculitis." Doctoral thesis, Università degli studi di Trento, 2021. http://hdl.handle.net/11572/325394.

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Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of B-cell driven, autoimmune systemic vasculitides characterized by a relapsing course and the presence of ANCA autoantibodies which are instrumental in their pathogenesis. We aimed to investigate autoreactive proteinase 3 (PR3+) B cells involved in the development of human AAV. We previously developed a customized flow-cytometry method to identify autoreactive B cells among cryopreserved peripheral blood mononuclear cells (PBMC), using labeled PR3, one of the main AAV autoantigens, as a ligand. We therefore used multicolor flow cytometry in combination with bioinformatics and functional in vitro studies on 1) baseline samples of PBMC from 154 well-characterized participants of the RAVE trial (NCT00104299) with severely active PR3-ANCA+ AAV (PR3-AAV) and myeloperoxidase (MPO)-AAV, and 27 healthy controls (HC); 2) samples of matched bone marrow (BM) and peripheral blood from 8 non-vasculitis patients; and 3) 148 longitudinal samples from 23 PR3-AAV patients of the RAVE trial. Clinical data and outcomes from the trial and medical records were correlated with PR3+ B cells (total and subsets). In brief, we identified and phenotypically characterized autoreactive B cells in AAV and healthy controls, reporting their perturbations among the different B cell subsets, and their functional ability to produce PR3-ANCA autoantibodies in vivo and in vitro. We reported their maturation through central and peripheral tolerance checkpoints from BM to peripheral blood, leading to an accumulation of atypical autoreactive PR3+ memory B cells in PR3-AAV patients but not in MPO-AAV and HC. We also described the longitudinal association between autoreactive plasmablast redetection after anti-B cell 13 targeted therapy with the main disease outcome, relapse. Overall, our findings suggest the presence of defective central antigen-independent and peripheral antigen-dependent checkpoints in patients in PR3-AAV, elucidating the selection process of autoreactive B cells, and their association with disease relapse.

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郑健 and Jian Zheng. "Generation of human allo-antigen specific CD4+ and CD8+ regulatory T cells with CD40-activated B cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46922969.

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44

Guy, Thomas Victor. "The roles of CD4 T cells and B cells in antitumour immunity." Thesis, The University of Sydney, 2016. http://hdl.handle.net/2123/15427.

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There have been great advances in clinical immunotherapies against cancer over the past two decades. Most recently, immunotherapies directed against immuno-inhibitory molecules such as CTLA4 and PD1 have led to major therapeutic breakthroughs, rapidly becoming an integral part of clinical practice. Yet we still lack complete understanding of how these therapies work, how to increase their efficacy, and how to limit their often life-threatening side effects. Furthermore, we lack comprehensive understanding of the immune landscape in cancer. Antitumour responses incorporate a large number of cell types with a complex range of differentiation states, which cannot be readily determined in patients. Mouse models are more suitable to explore specific mechanisms of antitumour immunity. The work in this thesis utilises tumour-specific T cells and B cells from five different transgenic mouse lines, to explore how their interactions influence murine tumour growth. A model of CD4+ T cell mediated antitumour immunity was established, in which regulatory T cell, CD8+ T cell or B cell populations could be co-transferred into tumour-bearing hosts to observe how their interactions influenced tumour clearance. In this model, CD4+ T cells and regulatory T cells recognise tumour antigen indirectly on antigen presenting cells within the tumour bed, rather than the malignant cells themselves, whereas B cells and CD8+ T cells are capable of direct antigen recognition. Indirect antigen recognition was sufficient to drive potent tumour rejection by naive CD4+ T cells adoptively transferred into immunodeficient mice bearing subcutaneous tumours. Tumour clearance was associated with extensive T cell proliferation and Th1 cytokine production, whereas delayed relapse observed in some animals was associated with conversion of CD4+ T cells into immunosuppressive regulatory T cells. Poor tumour clearance was observed when naive CD4+ T cells were co-transferred into tumour-bearing mice together with tumour-specific natural regulatory T cells. The role of B cells and antibodies in antitumour immunity is still not fully understood. In some human cancers, the presence of tumour-infiltrating B cells and tumour-specific antibodies correlates with prolonged survival, whereas both positive and negative effects have been reported in animal models. The primary immune role of B cells is to produce antibodies, but they can also influence T cell function via antigen presentation and, in some contexts, immune regulation. Here we describe the multifaceted role of tumour-specific B cells in an in vivo model, addressing their role in antibody production, antigen presentation and immune suppression, and identifying the contexts in which they function to inhibit or promote tumour growth. The number of lung metastases was significantly decreased in the presence of tumour-specific antibodies, with the amount of IgG2a/c correlating most closely with protection. In contrast, antibody was not protective against subcutaneous tumours, even in a prophylactic setting. In short-term experiments, B cells were capable of presenting tumour-derived antigen to CD4+T cells, although less efficiently than myeloid antigen presenting cells. The efficiency of B cell antigen-presentation was increased if B cells were activated, or when memory CD4+T cells were used in place of naive CD4+T cells. In long-term experiments, the presence of tumour-specific B cells reduced the number of high affinity tumour-specific CD4+ T cells, which in turn decreased their ability to eradicate subcutaneous tumours. Failure to eradicate tumours was also associated with an increased proportion of induced Foxp3+ regulatory T cells within the tumour-specific CD4+ T cell population. However, the absolute number of induced regulatory T cells was independent of number of tumour-specific B cells and tumour growth. Finally, four novel transplantable tumour lines were generated in order to address the cooperative role of CD4+ T cells and CD8+ T cells in anti-tumour immune responses. Recognition of tumour-derived antigen by transgenic CD4+ and CD8+ T cells was confirmed. In summary, a novel animal model was established to study cooperation between tumour antigen-specific CD4+ T cells, regulatory T cells, B cells and/or CD8+ T cells. For the first time, the dual antitumour and immunosuppressive functions of B cells were characterised within a single model. The results reported in this thesis advance our understanding of lymphocyte populations in antitumour immunity and can easily be adapted to study the effects of immune checkpoint inhibitors in a pre-clinical setting.

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Piperno, Nicolas. "Role of autocrine IL-13 producing B cells in plasma cell development." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40762.

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Recent studies have determined that IgE-producing B lymphocytes are present in the respiratory mucosa of patients with asthma and rhinitis, but not in respiratory mucosa of normal individuals. Our laboratory has shown that B lymphocytes in human nasal mucosa stain strongly for interleukin 13 (IL-13), a crucial cytokine for airway hyper-responsiveness and remodelling, and that inhibiting IL-13 decreases IgE secretion significantly in B cells. We sought to determine the role of IL-13 in sustaining IgE-producing B lymphocytes in the absence of a lymph node-like environment. Human B lymphocytes were isolated from tonsils and purified by means of rosetting with sheep RBCs. Purified B cells were transfected by NucleofectionTM with IL-13- or IL-13Rα1-gene specific siRNA or anti-IL-13 antibodies. They were then stimulated with the LTK4A1 fibroblast line transfected with CD40-ligand or anti-CD40 antibodies, and recombinant IL-4. Total mRNA was extracted, and plasma cell related genes were measured by means of real-time PCR. Proliferation and colony formation were also observed to determine phenotypical differences. IL-13 siRNA and anti-IL-13 decreases IgE secretion in stimulated cultured B cells. Anti-IL-13 treatment also markedly increases prdm1 and april mRNA transcripts. Anti-IL-13 treatment caused stimulated B cells to produce more colonies that were smaller in size compared to control. Blocking production of IL-13 through anti-IL-13 may trigger B cells to mature into short-lived plasma cells by increasing prdm1 and april. IL-13 may be an important autocrine factor for long-lived IgE-producing B lymphocytes, and therefore be the reason for sustained IgE in the airways. Des études récentes ont déterminé que les lymphocytes B produisant l’IgE sont présents dans la muqueuse respiratoire des patients avec l'asthme et le rhinite, mais pas dans la muqueuse respiratoire d'individus normaux. Notre laboratoire a démontré que les lymphocytes B dans la muqueuse nasale humaine sont marqués fortement pour l’interleukine 13 (IL-13), une cytokine cruciale pour l’hypersensibilité des voies respiratoires et le remodelage, et en inhibant l’IL-13, la sécrétion d’IgE est diminuée de façon significative dans les cellules B. Nous avons cherché à déterminer le rôle d'IL-13 dans la production prolongée d'IgE par les lymphocytes B dans l’absence d’un environnement ressemblant à un environnement d’un ganglion lymphatique. Des lymphocytes B humaines ont été isolés d’amygdales et purifiés avec une méthode qui utilise le sang de mouton. Les cellules B purifiées ont été transfecté avec la technologie NucleofectionTM avec du ARN interférent spécifique pour l’IL-13 ou son récepteur ou avec des anticorps anti-IL-13. Ils ont été ensuite stimulés avec une lignée cellulaire de fibroblast (LTK4A1) transfectée avec le ligand CD40 ou stimulés avec des anticorps anti-CD40, et du IL-4 recombinante. L’ARNm total a été extrait, et les gènes reliés avec des cellules plasmocytaires ont été mesurés par la PCR temps réel. La prolifération et la formation des colonies ont été aussi observées pour déterminer les différences phénotypiques. L’ARN interférent d’IL-13 et l’anti-IL-13 diminue la sécrétion d'IgE dans les cellules B stimulées. De plus, le traitement d’anti-IL-13 augmente nettement les transcriptions de prdm1 et d'april. Le traitement d’anti-IL-13 a causé les cellules B stimulées à produire plus de colonies qui étaient plus petites comparée aux cellules contrôles. En bloquant la production d'IL-13 avec des anticorps anti-IL-13, les cellules B peuvent préférentiellement m

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46

Ekici, Rifat. "B cells in Type 1 diabetes : studies on cell surface antibody binding." Licentiate thesis, Umeå universitet, Immunologi/immunkemi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-37376.

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Bergamin, Fabio. "Antigen-presenting cells and BAFF in porcine B-cell responses against FMDV /." Bern : [s.n.], 2007. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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48

Hine, Dominic William. "B cells as antigen-presenting cells in a model of rheumatoid arthritis." Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/2189.

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Rheumatoid arthritis (RA) is a multifaceted inflammatory autoimmune disease characterised by the infiltration of leukocytes into synovial joints leading to the destruction of articular cartilage and bone. Autoreactive CD4+ T cells producing inflammatory cytokines are implicated in disease pathogenesis. The clinical efficacy of B cell-depletion therapy is not dependent on clearance of autoantibodies suggesting a critical role for B cells as antigen presenting cells (APC). To elucidate the role of B cells in activating CD4+ T cells in RA, this project examined B cell- mediated antigen presentation to CD4+ T cells isolated from T cell receptor (TCR)-transgenic mice specific for the major arthritogenic epitope of the candidate cartilage autoantigen, aggrecan. This system allows for direct comparison of aggrecan-specific B cells to dendritic cells (DC) and other APC in order to identify any unique consequences of B cell antigen presentation and modulation of CD4+ T cell effector cytokine production. The data presented here show the activation, proliferation and effector function of CD4 T cells co- cultured with different APC in the presence of aggrecan and demonstrate key differences in B cell and DC production of disease-relevant cytokines. Crucially, aggrecan-specific B cells induced greater CD4+ T cell production of the pathogenic cytokine IFN-γ than DC, despite equivalent IL-2 production. The role of aggrecan-mediated activation of several pattern recognition receptors in this process was excluded using an in vitro detection system. However, the identification of a differential requirement for CD80 and CD86 during antigen presentation by B cells and DC suggested a role for co-stimulatory molecules at the APC-T cell interface in mediating B cell induction in CD4 T cell IFN-γ production. In summary, this work highlights the role of the CD80/86-CD28 pathway in mediating the observed differential induction of CD4+ T cell IFN-γ production by antigen-specific B cells and DC following aggrecan presentation.

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Scuderi, Richard. "G1-phase cyclin expression in neoplastic B cells /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-292-2/.

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50

Velez, Maria-Gabriela. "Development and function of allelically included B cells /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2008.

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Thesis (Ph.D. in Immunology) -- University of Colorado Denver, 2008. Typescript. Includes bibliographical references (leaves 153-162). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

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Dissertations / Theses on the topic 'B cells'

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