TLR9-mediated signals rescue B-cells from Fas-induced apoptosis via inactivation of caspases

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• 作者：Anikó ; Hancz^a ; Gá ; bor Koncz^b ; Dá ; niel Szili^a ; Gabriella Sá ; rmay^a ; ^b ; ^{sarmayg@elte.hu}
• 关键词：BAFF ; B-cell activating factor belonging to the tumor necrosis factor family ; BAFFR ; receptors for BAFF ; BCR ; B-cell receptor complex ; FADD ; Fas-associated death domain ; FAIM ; Fas apoptosis inhibitory molecule ; FLIP ; FLICE-inhibitory protein ; TNF ; tumor n
• 刊名：Immunology Letters
• 出版年：2012
• 期刊代码：115_01652478
• 类别：med
• 出版时间：30 March, 2012
• 卷：143
• 期：1
• 页码：77-84
• 文件大小：568 K

摘要

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.