B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40.
In mice transgenic for an autoantibody, self-reactive B cells have been shown to be eliminated upon interaction with membrane-bound self-antigens in the periphery as well as in the bone marrow, suggesting that both immature and mature B cells are eliminated by multimerization of surface immunoglobulins (sIg). Activation of mature B cells by antigens may thus require a second signal that inhibits sIg-mediated apoptosis. Such a second signal is likely to be provided by T helper cells, because B-cell tolerance is more easily induced in the absence of T helper cells. To assess the molecular nature of the signal that inhibits sIg-mediated apoptosis, we used anti-IgM-induced apoptotic death of WEHI-231 B lymphoma cells as a model system. Here we report that the signal for abrogating sIg-mediated apoptosis is generated by association of the CD40L molecule on T cells with the CD40 molecule on WEHI-231 cells. T-cell help through CD40 may thus determine whether B cells are eliminated or activated upon interaction with antigens.
Tsubata
T
T
Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.
Wu
J
J
Honjo
T
T
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens; D023201:CD40 Ligand; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand