title: Antigen receptor-mediated B cell death is blocked by signaling via CD72 or treatment with dextran sulfate and is defective in autoimmunity-prone mice.
abstract: Mature B cells undergo programmed cell death when surface (s) Ig is extensively multimerized. A signal that blocks death of B cells is thus required for activation of B cells in response to antigen stimulation. Here we show that only a few diverse transmembrane signals capable of inducing activation and proliferation of B cells blocked sig-mediated death of normal mature B cells, and that there is no correlation between mitogenic activity and the ability to rescue B cells from death. The results suggest that a specific signal is required for abrogating B cell death induced by sig cross-linking. Signaling via IL-4 receptor and CD40, both of which are derived from activated T cells, blocked sig-mediated death, as described previously. Signaling through a B cell antigen CD72, a counter-receptor of the pan-T antigen CD5, also blocked death of anti-Ig-treated mouse spleen B cells. CD72 signal may play a role in survival of B cells at the initial step of T-B interaction, where resting T cells recognize antigens presented by B cells. Moreover, B cell death by anti-Ig was blocked by T cell-independent antigens such as lipopolysaccharide and dextran sulfate, and spleen B cells from New Zealand mice, which are prone to autoantibody-dependent autoimmune diseases, were resistant to sig-mediated death. Mechanisms for blocking sig-mediated death may therefore be required in antibody response to foreign antigens regardless of T independence or T dependence and in autoantibody production.
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Kyoto 606, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: H
authors.initials: H
authors.lastname: Han
authors.forename: M C
authors.initials: MC
authors.lastname: Howard
authors.forename: H
authors.initials: H
authors.lastname: Yagita
authors.forename: H
authors.initials: H
authors.lastname: Yakura
authors.forename: T
authors.initials: T
authors.lastname: Honjo
authors.forename: T
authors.initials: T
authors.lastname: Tsubata
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000494:pharmacology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D019013:CD40 Antigens / Q000187:drug effects; D018956:CD5 Antigens / Q000187:drug effects; D016264:Dextran Sulfate / Q000494:pharmacology*; D004198:Disease Susceptibility; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000187:drug effects* / Q000378:metabolism; D018123:Receptors, Interleukin / Q000187:drug effects; D019948:Receptors, Interleukin-4; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D018956:CD5 Antigens; C064228:CD72 protein, human; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D016264:Dextran Sulfate