Chen W, Wang H G, Srinivasula S M, Alnemri E S, Cooper N R
H. Lee Moffitt Cancer Center and Research Institute, Department of Pharmacology and Therapeutics, University of South Florida, Tampa 33612, USA.
J Immunol. 1999 Sep 1;163(5):2483-91.
In contrast to positive signaling leading to proliferation, the mechanisms involved in negative signaling culminating in apoptosis after B cell Ag receptor (BCR) ligation have received little study. We find that apoptosis induced by BCR cross-linking on EBV-negative mature and immature human B cell lines involves the following sequential, required events: a cyclosporin A-inhibitable, likely calcineurin-mediated step; and activation of caspase-2, -3, and -9. Caspase-2 is activated early and plays a major role in the apoptotic pathway, while caspase-9 is activated later in the apoptotic pathway and most likely functions to amplify the apoptotic signal. Caspase-8 and -1, which are activated by ligation of the CD95 and TNF-R1 death receptors, are not involved. Apoptosis induced by BCR ligation thus proceeds via a previously unreported intracellular signaling pathway.
与导致增殖的正向信号传导相反，B细胞抗原受体（BCR）连接后最终导致细胞凋亡的负向信号传导所涉及的机制鲜有研究。我们发现，EBV阴性的成熟和未成熟人B细胞系上BCR交联诱导的细胞凋亡涉及以下连续的必要事件：一个环孢菌素A可抑制的、可能由钙调神经磷酸酶介导的步骤；以及半胱天冬酶-2、-3和-9的激活。半胱天冬酶-2早期被激活并在凋亡途径中起主要作用，而半胱天冬酶-9在凋亡途径后期被激活，最有可能起到放大凋亡信号的作用。由CD95和TNF-R1死亡受体连接激活的半胱天冬酶-8和-1不参与其中。因此，BCR连接诱导的细胞凋亡通过一条以前未报道的细胞内信号传导途径进行。
