Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP.
Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP.
复制标题
B 细胞抗原受体通过 c-FLIP 抑制 Fas 介导的细胞凋亡。
DOI：
10.1002/1521-4141(200001)30:1
复制
发表时间：
2000
影响因子：
5.4
通讯作者：
Lenardo,MJ
中科院分区：
文献类型：
--
作者：
Wang,J;Lobito,AA;Shen,F;Hornung,F;Winoto,A;Lenardo,MJ
B细胞抗原受体（BCR）的交联诱导对Fas（APO-1 /CD 95）依赖性细胞凋亡的抗性，从而调节抗原刺激期间B细胞选择的一种机制。为了研究BCR信号调节Fas通路的分子机制，我们检测了死亡诱导信号复合物（DISC）组分的表达，包括Fas，FADD，caspase-8和细胞FLICE抑制蛋白（c-FLIP）。BCR交联后，未观察到Fas、FADD或caspase-8的细胞水平发生显著变化。相比之下，在原代B细胞和两种B细胞系A20和WEHI-279中，长型c-FLIP（c-FLIPL）通过BCR交联显著上调。此外，将c-FLIPL转染到A20细胞中可抑制Fas依赖性凋亡，并抑制caspase-8向DISC的募集。BCR交联或FLIP过表达也可保护B细胞免受TRAIL诱导的凋亡。因此，BCR信号上调c-FLIPL并抑制Fas和TRAIL受体凋亡途径，这可能对抗原特异性B细胞的耐受和选择很重要。
Cross‐linking of the B cell antigen receptor (BCR) induces resistance to Fas (APO‐1 / CD95)‐dependent apoptosis and thereby regulates one mechanism of B cell selection during antigen stimulation. To investigate the molecular mechanism by which BCR signaling regulates the Fas pathway, we examined the expression of constituents of the death‐inducing signaling complex (DISC), including Fas, FADD, caspase‐8 and cellular FLICE‐inhibitory protein (c‐FLIP). No significant changes in the cellular levels of Fas, FADD or caspase‐8 were observed after BCR cross‐linking. By contrast, the long isoform of c‐FLIP (c‐FLIPL) was significantly up‐regulated by BCR cross‐linking in primary B cells and in two B cell lines, A20 and WEHI‐279. Moreover, transfection of c‐FLIPLinto A20 cells inhibited Fas‐dependent apoptosis and suppressed recruitment of caspase‐8 to the DISC. BCR cross‐linking or FLIP overexpression also protects B cells from TRAIL‐induced apoptosis. Thus, BCR signaling up‐regulates c‐FLIPLand suppresses the Fas‐ and TRAIL‐receptor apoptosis pathways which could be important for tolerance and selection of antigen‐specific B cells.