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-mediat...Continue Reading
References
Citations
Related Concepts
Related Feeds
B cell Activation
B cell activation is initiated by the ligation of the B cell receptor with antigen and ultimately results in the production of protective antibodies against potentially pathogenic invaders. Here is the latest research.
Apoptotic Caspases
Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis