B-lymphocyte contributions to human autoimmune disease.
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.
Yanaba
Koichi
K
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Bouaziz
Jean-David
JD
Matsushita
Takashi
T
Magro
Cynthia M
CM
St Clair
E William
EW
Tedder
Thomas F
TF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017951:Antigen Presentation / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D051379:Mice; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016753:Interleukin-10; D000069283:Rituximab