Cutting edge: Cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein protects germinal center B cells from apoptosis during germinal center reactions

During germinal center (GC) reactions, follicular dendritic cells are belie ved to select memory B lymphocytes by switching off apoptosis in the succes sfully binding B cells. The cellular signals involved in this process are l argely 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-c onverting enzyme-like inhibitory protein (cFLIP(L)), which is capable of in hibiting death receptor-induced caspase activation. In isolated GC B cells, cFLIP(L) decays rapidly even without Fas ligation, and this results in act ivation of caspase activity and apoptosis. Contact with follicular dendriti c cells prevents cFLIP(L) degradation and blocks all signs of apoptosis, ev en in the presence of anti-Fas Abs. cFLIP(L) expression is sustained by CD4 0 ligation as well, suggesting that at least at some stage of the GC reacti on activated T cells may help selected B cells to leave the follicular dend ritic cell network without becoming apoptotic.