title: TLR9-mediated signals rescue B-cells from Fas-induced apoptosis via inactivation of caspases.
abstract: The death receptor, CD95/Fas, serves to eliminate potentially dangerous, self-reactive B cells. Engagement of B-cell receptors (BCR) on mature B-cells mediates the escape from cell death resulting in the activation and expansion of antigen specific clones. In addition to the antigen receptors, the receptors of B-cell activating factor belong to the tumor necrosis factor (TNF) family (BAFFR); moreover, the pattern recognition receptor, TLR9 may also deliver survival signals inhibiting Fas-mediated death of B-cells. Our aim was to compare the mechanism of BCR-induced and the BAFFR- or TLR9-stimulated rescue of B-cells from CD95/Fas-mediated apoptosis. We have found that BAFFR and TLR9 collaborate with BCR to protect B-cells from Fas-induced elimination and the rescue is independent of protein synthesis. The results revealed that the TLR9- and BCR-triggered rescue signals are transmitted through partially overlapping pathways; the protein kinase C (PKC) and the abl kinase induced phosphorylation may inactivate caspases in both CpG and anti-IgG stimulated cells. However, PI3-K activation is crucial upon the BCR driven anti-apoptotic effect, while p38 MAPK-mediated inactivation of caspases seems to play essential role in TLR9-mediated protection against Fas-induced programmed cell death.
authors.affiliation: Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Anikó
authors.initials: A
authors.lastname: Hancz
authors.forename: Gábor
authors.initials: G
authors.lastname: Koncz
authors.forename: Dániel
authors.initials: D
authors.lastname: Szili
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sármay
mesh_terms: D000818:Animals; D017209:Apoptosis; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D051379:Mice; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology*
chemical_list: D053265:B-Cell Activation Factor Receptor; D011947:Receptors, Antigen, B-Cell; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D019014:fas Receptor; D020169:Caspases