NF-κB-mediated up-regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B lymphocytes
摘要：
Activation of CD40 is essential for thymus-dependent humoral immune responses and rescuing B cells from apoptosis. Many of the effects of CD40 are believed to be achieved through altered gene expression. In addition to Bcl-x, a known CD40-regulated antiapoptotic molecule, we identified a related antiapoptotic molecule, A1/Bfl-1, as a CD40-inducible gene. Inhibition of the NF-κ B pathway by overexpression of a dominant-active inhibitor of NF-κ B abolished CD40-induced up-regulation of both the Bfl-1 and Bcl-x genes and also eliminated the ability of CD40 to rescue Fas-induced cell death. Within the upstream promoter region of Bcl-x, a potential NF-κ B-binding sequence was found to support NF-κ B-dependent transcriptional activation. Furthermore, expression of physiological levels of Bcl-x protected B cells from Fas-mediated apoptosis in the absence of NF-κ B signaling. Thus, our results suggest that CD40-mediated cell survival proceeds through NF-κ B-dependent up-regulation of Bcl-2 family members.
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DOI：
10.1073/pnas.96.16.9136
被引量：
年份：
1999
国家科技图书文献中心
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掌桥科研
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