Intracellular signaling for inducible antigen receptor-mediated Fas resistance in B cells.
CD40 ligand-activated B cells are sensitive targets for CD4+ Th1 effector cells that kill in a Fas-dependent fashion. Susceptibility to apoptosis is counteracted by Ag receptor binding that produces a state of resistance to Fas engagement in otherwise sensitive targets. In the present study, protection from Th1-mediated apoptosis was found to be induced by protein kinase C and calcium signals, which in combination mimicked the level of Fas resistance produced by surface Ig engagement. Signaling for Fas resistance did not alter Fas expression. Furthermore, B cells that were protected against Th1-mediated apoptosis were also resistant to apoptosis mediated by soluble, rFas ligand. Taken together, these results indicate that signaling for protection against Fas-mediated apoptosis does not depend on alteration of the interaction between B cell target and Th1 effector populations. Instead, surface IgM-derived protein kinase C and calcium signals appear to produce an intracellular change in the Fas signaling pathway that develops over a period of hours and interferes with the apoptotic process through a mechanism that depends on protein synthesis.
Foote
L C
LC
Department of Microbiology, Evans Memorial Department of Clinical Research, Boston University Medical Center, MA 02118, USA.
Schneider
T J
TJ
Fischer
G M
GM
Wang
J K
JK
Rasmussen
B
B
Campbell
K A
KA
Lynch
D H
DH
Ju
S T
ST
Marshak-Rothstein
A
A
Rothstein
T L
TL
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004338:Drug Combinations; D007075:Immunoglobulin M / Q000276:immunology; D007424:Intracellular Fluid / Q000276:immunology; D015759:Ionomycin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000201:enzymology / Q000276:immunology; D019014:fas Receptor / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D004338:Drug Combinations; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; C044203:anti-IgM; D019014:fas Receptor; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate