TGFB induces apoptosis in human B cells via transcriptional regulation of BIK and BCL-XL

The contribution of TGF-β signaling to regulation of BCL-2 family members is included alongside known apoptosis pathways functional in germinal centres. The three separate apoptosis pathways converge to regulate death of human centroblasts. FAS signaling activates the extrinsic caspase-8/caspase-3 cascade while TGF-β signaling via its receptor complex represses the prosurvival factor BCL-XL and induces BIK to activate the intrinsic pathway. Fas and TGF-β signaling contribute to the default apoptotic state of ‘death by neglect’ while B cell receptor signaling also activates the mitochondrial apoptosis pathway in cells lacking environmental survival cues. Loss of TGF-β signaling through inhibition of TGF-β receptor signaling by SB-431542 would reduce the amount of caspase-3 activation and raise the threshold for apoptosis induction. The model highlights the requirement for maintenance of cFLIP and BCL-XL levels for cells to survive during germinal centre reactions.

Publication

TGF-β induces apoptosis in human B cells via transcriptional regulation of BIK and BCL-XL. () LC Spender, et al. Cell Death Differ. ;16(4):593-602. Figure: F7. Homo sapiens

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