TY - JOUR
T1 - Inhibition of Fas-mediated apoptosis by the B cell antigen receptor through c-FLIP
AU - Wang, Jin
AU - Lobito, Adrian A.
AU - Shen, Fan
AU - Hornung, Felicita
AU - Winoto, Astar
AU - Lenardo, Michael J.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
KW - Apoptosis
KW - B lymphocyte
KW - c-FLIP
UR - http://www.scopus.com/inward/record.url?scp=0033989612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033989612&partnerID=8YFLogxK
U2 - 10.1002/1521-4141(200001)30:1<155::AID-IMMU155>3.0.CO;2-X
DO - 10.1002/1521-4141(200001)30:1<155::AID-IMMU155>3.0.CO;2-X
M3 - Article
C2 - 10602037
AN - SCOPUS:0033989612
SN - 0014-2980
VL - 30
SP - 155
EP - 163
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 1
ER -