Yamashita Y, Miyake K, Miura Y, Kaneko Y, Yagita H, Suda T, Nagata S, Nomura J, Sakaguchi N, Kimoto M
Department of Immunology, Saga Medical School, Japan.
J Exp Med. 1996 Jul 1;184(1):113-20. doi: 10.1084/jem.184.1.113.
Signals through the B cell antigen receptor lead to a variety of cellular events such as activation, anergy, and apoptosis. B cells select these outcomes to establish and maintain self-tolerance, and to mount adequate antibody responses. However, it is not fully understood how one and the same signal causes such different consequences. In the present study, we have studied the effect of activation signals on the outcome of responses to antigen receptor ligation. Two distinct growth-promoting signals were used to activate B cells. Ligation of either RP105, a newly discovered B cell surface molecule, or the CD40 molecule, drove B cells to proliferate. Resultant blastic cells were then exposed to anti-immunoglobulin M (IgM). Blast cells that had been stimulated with anti-RP105 ceased growing and underwent apoptosis after cross-linking of surface IgM. Coligation of the Fc gamma receptor IIB with surface IgM augmented, rather than aborted, this response. In contrast to RP105-activated B cells, blast cells that had been activated by CD40 ligation were unaltered by anti-IgM. On the other hand, CD40-activated B cells became extremely susceptible to Fas-mediated apoptosis, whereas RP105-activated B cells were much less sensitive. Anti-IgM-induced apoptosis in RP105 blasts was independent of Fas, because it was demonstrable with Fas-deficient MRL-lpr/lpr mice. These results demonstrate that the nature of an initial activation signal has a great influence on the fate of activated B cells after (re)engagement of the antigen receptor. RP105, as well as CD40, may be important in this life/death decision.
通过B细胞抗原受体传导的信号会引发多种细胞事件，如激活、无反应性和凋亡。B细胞选择这些结果以建立和维持自身耐受性，并产生充分的抗体反应。然而，目前尚不完全清楚同一信号如何导致如此不同的后果。在本研究中，我们研究了激活信号对抗抗原受体连接反应结果的影响。使用两种不同的促生长信号来激活B细胞。新发现的B细胞表面分子RP105或CD40分子的连接均可驱动B细胞增殖。然后将由此产生的母细胞暴露于抗免疫球蛋白M（IgM）。用抗RP105刺激的母细胞在表面IgM交联后停止生长并发生凋亡。Fcγ受体IIB与表面IgM的共连接增强而非终止了这种反应。与RP105激活的B细胞不同，由CD40连接激活的母细胞不受抗IgM的影响。另一方面，CD40激活的B细胞变得极易受到Fas介导的凋亡影响，而RP105激活的B细胞则不太敏感。抗IgM诱导的RP105母细胞凋亡与Fas无关，因为在Fas缺陷的MRL-lpr/lpr小鼠中也可观察到这种现象。这些结果表明，初始激活信号的性质对抗抗原受体（重新）连接后活化B细胞的命运有很大影响。RP105以及CD40在这种生死抉择中可能很重要。
