caa a22 4500 605543968 CHVBK 20210128100929.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00109-015-1252-8 doi (NATIONALLICENCE)springer-10.1007/s00109-015-1252-8 Signaling mechanisms regulating B-lymphocyte activation and tolerance [Elektronische Daten] [Elias Hobeika, Peter Nielsen, David Medgyesi] 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. Springer-Verlag Berlin Heidelberg, 2015 B lymphocyte nationallicence B-cell tolerance nationallicence Autoimmunity nationallicence Inhibitory signaling nationallicence Hobeika Elias BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany aut Nielsen Peter BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany aut Medgyesi David BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany aut Journal of Molecular Medicine Springer Berlin Heidelberg 93/2(2015-02-01), 143-158 0946-2716 93:2<143 2015 93 109 https://doi.org/10.1007/s00109-015-1252-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00109-015-1252-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hobeika Elias BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany aut NATIONALLICENCE 700 1- Nielsen Peter BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany aut NATIONALLICENCE 700 1- Medgyesi David BIOSS Centre of Biological Signalling Studies, University of Freiburg and Department for Molecular Immunology, Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany aut NATIONALLICENCE 773 0- Journal of Molecular Medicine Springer Berlin Heidelberg 93/2(2015-02-01), 143-158 0946-2716 93:2<143 2015 93 109