Translational Mini-Review Series on B Cell-Directed Therapies: B cell-directed therapy for autoimmune diseases

Hu, C.; Wong, F. Susan; Li, Wen

doi:10.1111/j.1365-2249.2009.03977.x

Cited by 8 publications

(3 citation statements)

References 108 publications

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“…Indeed, B cells efficiently present antigens,4 act as costimulators during the initiation of immune responses,5‐7 and secrete cytokines 3, 8‐10. Not surprisingly, this increased awareness of the importance of B cells in the pathogenesis of autoimmunity has led to the development of novel B cell–targeted biological therapies 11‐15…”

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confidence: 99%

B cell depletion therapy exacerbates murine primary biliary cirrhosis

et al. 2010

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Primary biliary cirrhosis (PBC) is considered a model autoimmune disease due to the clinical homogeneity of patients and the classic hallmark of antimitochondrial antibodies (AMAs). Indeed, the presence of AMAs represents the most highly directed and specific autoantibody in autoimmune diseases. However, the contribution of B cells to the pathogenesis of PBC is unclear. Therefore, although AMAs appear to interact with the biliary cell apotope and contribute to biliary pathology, there is no correlation of disease severity and titer of AMAs. The recent development of well-characterized monoclonal antibodies specific for the B cell populations, anti-CD20 and anti-CD79, and the development of a welldefined xenobiotic-induced model of autoimmune cholangitis prompted us to use these reagents and the model to address the contribution of B cells in the pathogenesis of murine PBC. Prior to the induction of autoimmune cholangitis, mice were treated with either anti-CD20, anti-CD79, or isotype-matched control monoclonal antibody and followed for B cell development, the appearance of AMAs, liver pathology, and cytokine production. Results of the studies reported herein show that the in vivo depletion of B cells using either anti-CD20 or anti-CD79 led to the development of a more severe form of cholangitis than observed in control mice, which is in contrast with results from several other autoimmune models that have documented an important therapeutic role of B cell-specific depletion. Anti-CD20/CD79-treated mice had increased liver T cell infiltrates and higher levels of proinflammatory cytokines. Conclusion: Our results reflect a novel disease-protective role of B cells in PBC and suggest that B cell depletion therapy in humans with PBC should be approached with caution (HEPATOLOGY 2011;53:527-535)

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confidence: 99%

B cell depletion therapy exacerbates murine primary biliary cirrhosis

et al. 2010

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“…Among the most widely used B cell-depleting agents are those that target the CD20 molecule expressed on essentially all mature B cells [ 100 , 101 ]. Rituximab, directed against CD20 on human B cells, has been used to treat autoimmune diseases in humans [ 102 , 103 , 104 ] and antibody specific for mouse CD20 has been used to prevent or treat autoimmune diseases in many mouse models [ 3 , 13 , 14 , 25 , 41 , 42 , 61 , 105 , 106 ]. The effectiveness of anti-CD20 for suppression of autoimmune disease varies in different mouse models and human diseases, and several factors that influence the effectiveness of B cell depletion are briefly reviewed here.…”

Section: Multiple Factors Influence the Effectiveness Of B Cell Dementioning

confidence: 99%

Mechanisms by Which B Cells and Regulatory T Cells Influence Development of Murine Organ-Specific Autoimmune Diseases

Ellis

Braley‐Mullen

2017

JCM

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Experiments with B cell-deficient (B−/−) mice indicate that a number of autoimmune diseases require B cells in addition to T cells for their development. Using B−/− Non-obese diabetic (NOD) and NOD.H-2h4 mice, we demonstrated that development of spontaneous autoimmune thyroiditis (SAT), Sjogren’s syndrome and diabetes do not develop in B−/− mice, whereas all three diseases develop in B cell-positive wild-type (WT) mice. B cells are required early in life, since reconstitution of adult mice with B cells or autoantibodies did not restore their ability to develop disease. B cells function as important antigen presenting cells (APC) to initiate activation of autoreactive CD4+ effector T cells. If B cells are absent or greatly reduced in number, other APC will present the antigen, such that Treg are preferentially activated and effector T cells are not activated. In these situations, B−/− or B cell-depleted mice develop the autoimmune disease when T regulatory cells (Treg) are transiently depleted. This review focuses on how B cells influence Treg activation and function, and briefly considers factors that influence the effectiveness of B cell depletion for treatment of autoimmune diseases.

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“…Medical science has learned, over the course of the developmental history of vaccination, how to present antigenic components in an inoculate to stimulate protective immune responses in the vaccinated host against exogenous ags. However, the possibility of using vaccination to achieve protective or curative outcomes in patients with disorders caused by endogenous ags, without causing side effects, has remained elusive (Ben Yehuda et al, 1988;Fox & McCune, 1994;Golbus & McCune, 1994;Hu et al, 2009;Nepom, 2002;Perosa et al, 2005;Thaiss et al, 1989). Our investigations into the etiology and pathogenesis of an experimental autoimmune kidney disease have resulted in a new immunological approach involving the presentation of native autoimmune disease related ags to evoke a predetermined corrective immune response in the host (Barabas et al, 2004b;Barabas et al, 2006c;Barabas et al, 2006b;Barabas & Lafreniere, 2005).…”

Section: Introductionmentioning

confidence: 99%