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Signaling mechanisms regulating B-lymphocyte activation and tolerance

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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.

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Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft through SFB746 and TRR130.

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  1. BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany

    Elias Hobeika, Peter J. Nielsen & David Medgyesi

  2. Max Planck Institute of Immunobiology and Epigenetics, 79108, Freiburg, Germany

    Elias Hobeika, Peter J. Nielsen & David Medgyesi

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Hobeika, E., Nielsen, P.J. & Medgyesi, D. Signaling mechanisms regulating B-lymphocyte activation and tolerance. J Mol Med 93, 143–158 (2015). https://doi.org/10.1007/s00109-015-1252-8

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