Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP

Jin Wang, Adrian A. Lobito, Fan Shen, Felicita Hornung, Astar Winoto, Michael J. Lenardo

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

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-FLIP(L)) 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-FLIP(L) into 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-FLIP(L) and suppresses the Fas- and TRAIL-receptor apoptosis pathways which could be important for tolerance and selection of antigen-specific B cells.

Original languageEnglish (US)
Pages (from-to)155-163
Number of pages9
JournalEuropean Journal of Immunology
Volume30
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Apoptosis
  • B lymphocyte
  • c-FLIP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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