B-lymphocyte contributions to human autoimmune disease

Authors



Thomas F. Tedder
Department of Immunology
Duke University Medical Center
Box 3010
Durham, NC 27710, USA
Tel.: +1 919 684 3578
Fax: +1 919 684 8982
e-mail: thomas.tedder@duke.edu

Abstract

Summary: Autoimmunity results from abnormal B- and T-cell recognition of self-antigens, which leads to autoantibody production in many cases. Autoantibodies produced by B-cell-derived plasma cells provide diagnostic markers for autoimmunity but also contribute significantly to disease pathogenesis. As discussed in this review, the therapeutic benefit of depleting B cells in mice and humans has refocused attention on B cells and their role in autoimmunity beyond autoantibody production. B cells specifically serve as cellular adjuvants for CD4+ T-cell activation, while regulatory B cells, including those that produce interleukin-10 (B10 cells), function as negative regulators of inflammatory immune responses. The emerging picture is that B cells, autoantibodies, and T cells are all important components of abnormal immune responses that lead to tissue pathology unique to each autoimmune disease, with their relative contributions changing during disease progression. Autoimmune diseases where B-cell functions are closely correlated with disease activity include systemic lupus erythematosus, rheumatoid arthritis, scleroderma, type 1 diabetes, and multiple sclerosis. Understanding the overlapping roles of B cells as mediators of autoimmune disease will facilitate the development of more precisely directed therapies and combination therapies with broader clinical efficacy than current depletion strategies that remove all B cells.

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