Cooperation of B cells and T cells in the pathogenesis of multiple sclerosis.
B cells and T cells are two major players in the pathogenesis of multiple sclerosis (MS) and cooperate at various check points. B cells, besides serving as a source for antibody-secreting plasma cells, are efficient antigen presenting cells for processing of intact myelin antigen and subsequent activation and pro-inflammatory differentiation of T cells. This notion is supported by the immediate clinical benefit of therapeutic B cell depletion in MS, presumably abrogating development of encephalitogenic T cells. However, different B cell subsets strongly vary in their respective effect on T cell differentiation which may relate to B cell phenotype, activation status, antigen specificity and the immunological environment where a B cell encounters a naïve T cell in. In this regard, some B cells also have anti-inflammatory properties producing regulatory cytokines and facilitating development and maintenance of other immunomodulatory immune cells, such as regulatory T cells. Reciprocally, differentiated T cells influence T cell polarizing B cell properties establishing a positive feedback loop of joint pro- or anti-inflammatory B and T cell developments. Further, under the control of activated T helper cells, antigen-primed B cells can switch immunoglobulin isotype, terminally commit to the plasma cell pathway or enter the germinal center reaction to memory B Cell development. Taken together, B cells and T cells thus closely support one another to participate in the pathogenesis of MS in an inflammatory but also in a regulatory manner.
Weber
Martin S
MS
Department of Neurology, Technische Universität München, Ismaningerstrasse 22, 81675, Munich, Germany.
Hemmer
Bernhard
B
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008212:Lymphocyte Depletion; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D010950:Plasma Cells / Q000276:immunology; D000069283:Rituximab; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab