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Alexander M Owyang, Joseph R Tumang, Brian R Schram, Constance Y Hsia, Timothy W Behrens, Thomas L Rothstein, Hsiou-Chi Liou, c-Rel Is Required for the Protection of B Cells from Antigen Receptor-Mediated, But Not Fas-Mediated, Apoptosis, The Journal of Immunology, Volume 167, Issue 9, November 2001, Pages 4948–4956, https://doi.org/10.4049/jimmunol.167.9.4948
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Abstract
The NF-κB/Rel transcription factor family has been shown to protect many cell types from apoptotic signals. However, it is not known whether NF-κB is required for all survival pathways and whether each NF-κB member plays a unique or a redundant role. Here we describe the results of studies on the role of c-Rel in survival. Mature B cells from c-Rel−/− mice exhibit defects in survival, including sensitivity to Ag receptor-mediated apoptosis as well as increased sensitivity to ionizing radiation and glucocorticoids. Transgene expression of Bcl-xL, a c-Rel target gene, rescues c-Rel−/− B cells from their survival defects. Thus, c-Rel-dependent survival pathways are crucial for protection from apoptotic signals that target the mitochondrial pathway. Despite a lack of Bcl-xL, c-Rel−/− B cells can still be rescued from Fas-mediated apoptosis via B cell receptor signaling. The Fas apoptosis inhibitor molecule and FLICE inhibitory protein (c-FLIP) proteins are up-regulated normally in c-Rel−/− B cells, and these two molecules may play a more physiological role in the Fas pathway. Furthermore, unlike the TNF sensitivity of RelA−/− fibroblasts, c-Rel-deficient fibroblasts are refractory to TNF-mediated cell death. Thus, c-Rel is dispensable for protection against death receptor-mediated apoptosis. Taken together, our data suggest that distinct NF-κB/Rel members are required for protecting cells from different types of apoptotic signals.
