Foote L C, Schneider T J, Fischer G M, Wang J K, Rasmussen B, Campbell K A, Lynch D H, Ju S T, Marshak-Rothstein A, Rothstein T L
Department of Microbiology, Evans Memorial Department of Clinical Research, Boston University Medical Center, MA 02118, USA.
J Immunol. 1996 Sep 1;157(5):1878-85.
CD40 ligand-activated B cells are sensitive targets for CD4+ Th1 effector cells that kill in a Fas-dependent fashion. Susceptibility to apoptosis is counteracted by Ag receptor binding that produces a state of resistance to Fas engagement in otherwise sensitive targets. In the present study, protection from Th1-mediated apoptosis was found to be induced by protein kinase C and calcium signals, which in combination mimicked the level of Fas resistance produced by surface Ig engagement. Signaling for Fas resistance did not alter Fas expression. Furthermore, B cells that were protected against Th1-mediated apoptosis were also resistant to apoptosis mediated by soluble, rFas ligand. Taken together, these results indicate that signaling for protection against Fas-mediated apoptosis does not depend on alteration of the interaction between B cell target and Th1 effector populations. Instead, surface IgM-derived protein kinase C and calcium signals appear to produce an intracellular change in the Fas signaling pathway that develops over a period of hours and interferes with the apoptotic process through a mechanism that depends on protein synthesis.
CD40配体激活的B细胞是CD4 + Th1效应细胞以Fas依赖方式杀伤的敏感靶标。抗原受体结合可抵消细胞凋亡敏感性，在其他敏感靶标中产生对Fas结合的抗性状态。在本研究中，发现蛋白激酶C和钙信号可诱导对Th1介导的细胞凋亡的保护作用，二者共同作用模拟了表面Ig结合产生的Fas抗性水平。Fas抗性信号传导并未改变Fas表达。此外，免受Th1介导的细胞凋亡保护的B细胞对可溶性rFas配体介导的细胞凋亡也具有抗性。综上所述，这些结果表明，针对Fas介导的细胞凋亡的保护信号传导不依赖于B细胞靶标与Th1效应细胞群体之间相互作用的改变。相反，表面IgM衍生的蛋白激酶C和钙信号似乎在Fas信号通路中产生细胞内变化，这种变化在数小时内发展，并通过一种依赖于蛋白质合成的机制干扰凋亡过程。
