van Eijk M, Medema J P, de Groot C
Department of Cell Biology and Histology, Cellular Immunology Group, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
J Immunol. 2001 Jun 1;166(11):6473-6. doi: 10.4049/jimmunol.166.11.6473.
During germinal center (GC) reactions, follicular dendritic cells are believed to select memory B lymphocytes by switching off apoptosis in the successfully binding B cells. The cellular signals involved in this process are largely unknown. Here, we show that GC B lymphocytes have a long isoform of the cellular homologue of the viral Fas-associated death domain-like IL-1-converting enzyme-like inhibitory protein (cFLIP(L)), which is capable of inhibiting death receptor-induced caspase activation. In isolated GC B cells, cFLIP(L) decays rapidly even without Fas ligation, and this results in activation of caspase activity and apoptosis. Contact with follicular dendritic cells prevents cFLIP(L) degradation and blocks all signs of apoptosis, even in the presence of anti-Fas ABS: cFLIP(L) expression is sustained by CD40 ligation as well, suggesting that at least at some stage of the GC reaction activated T cells may help selected B cells to leave the follicular dendritic cell network without becoming apoptotic.
在生发中心（GC）反应过程中，滤泡树突状细胞被认为是通过关闭成功结合的B细胞中的凋亡来选择记忆B淋巴细胞的。参与这一过程的细胞信号在很大程度上尚不清楚。在此，我们表明GC B淋巴细胞具有病毒Fas相关死亡结构域样白细胞介素-1转换酶样抑制蛋白（cFLIP(L)）的细胞同源物的长异构体，其能够抑制死亡受体诱导的半胱天冬酶激活。在分离的GC B细胞中，即使没有Fas连接，cFLIP(L)也会迅速降解，这导致半胱天冬酶活性激活和细胞凋亡。与滤泡树突状细胞接触可防止cFLIP(L)降解并阻断所有凋亡迹象，即使在存在抗Fas抗体的情况下也是如此：cFLIP(L)的表达也通过CD40连接得以维持，这表明至少在GC反应的某些阶段，活化的T细胞可能有助于选定的B细胞离开滤泡树突状细胞网络而不发生凋亡。
