title: Signaling mechanisms regulating B-lymphocyte activation and tolerance.
abstract: It is becoming more and more accepted that, in addition to producing autoantibodies, B lymphocytes have other important functions that influence the development of autoimmunity. For example, autoreactive B cells are able to produce inflammatory cytokines and activate pathogenic T cells. B lymphocytes can react to extracellular signals with a range of responses from anergy to autoreactivity. The final outcome is determined by the relative contribution of signaling events mediated by activating and inhibitory pathways. Besides the B cell antigen receptor (BCR), several costimulatory receptors expressed on B cells can also induce B cell proliferation and survival, or regulate antibody production. These include CD19, CD40, the B cell activating factor receptor, and Toll-like receptors. Hyperactivity of these receptors clearly contributes to breaking B-cell tolerance in several autoimmune diseases. Inhibitors of these activating signals (including protein tyrosine phosphatases, deubiquitinating enzymes and several adaptor proteins) are crucial to control B-cell activation and maintain B-cell tolerance. In this review, we summarize the inhibitory signaling mechanisms that counteract B-cell activation triggered by the BCR and the coreceptors.
authors: BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany.
authors: Elias
authors: E
authors: Hobeika
authors: Peter J
authors: PJ
authors: Nielsen
authors: David
authors: D
authors: Medgyesi
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D056747:Immunomodulation / Q000187:drug effects; D008213:Lymphocyte Activation / Q000276:immunology*; D058990:Molecular Targeted Therapy; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011947:Receptors, Antigen, B-Cell; D011971:Receptors, Immunologic
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