Antigen receptor-mediated B cell death is blocked by signaling via CD72 or treatment with dextra n sulfate and is defective in autoimmunity-prone mice

Abstract

Mature B cells undergo programmed cell death when surface (s) Ig is extensively multlmerized. 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 slg-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 slg cross-linking. Signaling via IL-4 receptor and CD40, both of which are derived from activated T cells, blocked slg-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-lg-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-lg 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 slg-mediated death. Mechanisms for blocking slg-mediated death may therefore be required in antibody response to foreign antigens regardless of T independence or T dependence and In autoantibody production.