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

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

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

机译：增加的MTOR抵消了在IL-1α缺陷B细胞中减少XBP-1对抗体分泌的影响

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IL-1 alpha in vitro promotes immunoglobulin secretion by inducing proliferation of mature B cells, whereas IL-1 alpha deficiency has no effect on in vivo antibody production. However, the reason IL-1 alpha deficiency does not reduce in vivo antibody production is still unclear. In this study, we found that similar as in vivo data, IL-1 alpha deficiency did not affect antibody production in in vitro LPS-stimulated B cells. Surprisingly, LPS-stimulated IL-1 alpha(-/-) B cells reduced a key antibody production-related transcription factor X-box binding protein 1 (Xbp-1) expression. Furthermore, we found that IL-1 alpha 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-1 alpha deficiency has no effect on antibody production.

机译：IL-1α在体外通过诱导成熟B细胞增殖促进免疫球蛋白分泌，而IL-1α缺乏对体内抗体产生没有影响。然而，IL-1α缺乏不能减少体内抗体产生的原因仍不清楚。在这项研究中，我们发现，与体内数据类似，IL-1α缺乏并不影响LPS刺激的B细胞体外产生抗体。令人惊讶的是，LPS刺激的IL-1α（-/-）B细胞降低了一个关键的抗体产生相关转录因子X盒结合蛋白1（Xbp-1）的表达。此外，我们发现IL-1α缺乏可上调mTOR表达，从而绕过Xbp-1分泌免疫球蛋白。最后，我们发现Xbp-1抑制mTOR表达，而mTOR通过JunB抑制Xbp-1启动子的激活。总之，这些数据表明IL-1a缺乏降低了Xbp-1并上调了mTOR。这可以解释为什么IL-1α缺乏对抗体产生没有影响。

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《Cellular immunology》 |2018年第2018期|共9页
作者
Zhu Gaizhi; Liu Xiaoling; Fang Ying; Zhai Bing; Xu Ruonan; Han Gencheng; Chen Guojiang; Xiao He; Hou Chunmei; Shen Beifen; Li Yan; Iwakura Yoichiro; Wang Liang; Jiang Zhenyu; Ma Ning; Liu Guangchao; Wang Renxi;
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作者单位

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

Tokyo Univ Sci Res Inst Biomed Sci Ctr Anim Dis Models 2669 Yamazalci Noda Chiba 2780022 Japan;

Xinjiang Univ Coll Life Sci &

Technol Urumqi 830046 Xinjiang Peoples R China;

307th Hosp Chinese Peoples Liberat Army Dept Nephrol Beijing 100850 Peoples R China;

Jilin Univ Dept Rheumatol Hosp 1 Xinming Str 71 Changchun 130021 Jilin Peoples R China;

Henan Univ Joint Natl Lab Antibody Drug Engn Jinming St Kaifeng 475004 Henan Peoples R China;

Inst Basic Med Sci Lab Immunol POB 130 3 Taiping Rd 27 Beijing 100850 Peoples R China;

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原文格式 PDF
正文语种 eng
中图分类细胞生物学;
关键词
IL-1 alpha; B cells; Antibody; Xbp-1; mTOR;

机译：IL-1α;B细胞;抗体;XBP-1;MTOR;

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机译：增加的MTOR抵消了XBP-1对IL-1缺乏B细胞中抗体分泌的效果
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Increased mTOR cancels out the effect of reduced Xbp-1 on antibody secretion in IL-1 alpha-deficient B cells

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