Increased mTOR cancels out the effect of reduced Xbp-1 on antibody secretion in IL-1α-deficient B cells

mTOR 增加可抵消 Xbp-1 减少对 IL-1α 缺乏的 B 细胞中抗体分泌的影响

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作者:Gaizhi Zhu, Xiaoling Liu, Ying Fang, Bing Zhai, Ruonan Xu, Gencheng Han, Guojiang Chen, He Xiao, Chunmei Hou, Beifen Shen, Yan Li, Yoichiro Iwakura, Liang Wang, Zhenyu Jiang, Ning Ma, Guangchao Liu, Renxi Wang

Abstract

IL-1α in vitro promotes immunoglobulin secretion by inducing proliferation of mature B cells, whereas IL-1α deficiency has no effect on in vivo antibody production. However, the reason IL-1α deficiency does not reduce in vivo antibody production is still unclear. In this study, we found that similar as in vivo data, IL-1α deficiency did not affect antibody production in in vitro LPS-stimulated B cells. Surprisingly, LPS-stimulated IL-1α-/- B cells reduced a key antibody production-related transcription factor X-box binding protein 1 (Xbp-1) expression. Furthermore, we found that IL-1α deficiency up-regulated mTOR expression, which bypassed Xbp-1 for immunoglobulin secretion. Finally, we showed that Xbp-1 suppressed mTOR expression, whereas mTOR suppressed the activation of Xbp-1 promoter via JunB. Together, these data suggest that IL-1a deficiency reduced Xbp-1 and up-regulated mTOR. This may explain why IL-1α deficiency has no effect on antibody production.

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