The flip side of Fas

Abstract

Developing lymphocytes are the rebellious youth of the immune system, walking a thin line between self-protective and self-destructive tendencies and submitting to tests of mettle in their overly protective environments. Immature T- and B cells are both given a narrow window of opportunity during development in which to avoid their demise and ‘prove’ their usefulness via successful receptor interactions. Adolescent B cells become vulnerable to selective processes yet again during affinity maturation in the germinal center (GC). The mechanism responsible for B-cell vulnerability to apoptosis in the GC microenvironment is debatable, but two recent papers revive a previously discarded hypothesis that the death receptor Fas (CD95) plays a role.Fas, which is expressed at relatively high levels on GC B cells, initiates apoptotic signals that activate Fas-associated death domain protein (FADD)-like interleukin-1β-converting enzyme (FLICE/caspase-8). Hennino et al. show that purified human GC B cells die rapidly in culture in a FLICE-dependent fashion and implicate an inhibitor of Fas signaling, c-FLICE-like inhibitory protein (c-FLIP), as the crucial regulator of GC B-cell death 1xFLICE-inhibitory protein is a key regulator of germinal center B-cell apoptosis. Hennino, A. et al. J. Exp. Med. 2001; 193: 447–458Crossref | PubMed | Scopus (108)See all