title: Intracellular signaling for inducible antigen receptor-mediated Fas resistance in B cells.
abstract: 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.
authors: Department of Microbiology, Evans Memorial Department of Clinical Research, Boston University Medical Center, MA 02118, USA.
authors: L C
authors: LC
authors: Foote
authors: T J
authors: TJ
authors: Schneider
authors: G M
authors: GM
authors: Fischer
authors: J K
authors: JK
authors: Wang
authors: B
authors: B
authors: Rasmussen
authors: K A
authors: KA
authors: Campbell
authors: D H
authors: DH
authors: Lynch
authors: S T
authors: ST
authors: Ju
authors: A
authors: A
authors: Marshak-Rothstein
authors: T L
authors: TL
authors: Rothstein
mesh_terms: 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*
chemical_list: 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