PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development

Mei Yu; Yuhong Chen; Hu Zeng; Yongwei Zheng; Guoping Fu; Wen Zhu; Ulrich Broeckel; Praful Aggarwal; Amy Turner; Geoffrey Neale; Cliff Guy; Nan Zhu; Hongbo Chi; Renren Wen; Demin Wang

doi:10.1038/s41467-017-01388-5

PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development

Mei Yu, Yuhong Chen, Hu Zeng, Yongwei Zheng, Guoping Fu, Wen Zhu, Ulrich Broeckel, Praful Aggarwal, Amy Turner, Geoffrey Neale, Cliff Guy, Nan Zhu, Hongbo Chi, Renren Wen, Demin Wang

Rheumatology

Research output: Contribution to journal › Article

6 Scopus citations

Abstract

The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B cell stage and renders B cell progenitors unresponsive to IL-7. PLCγ pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCγ pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis. Inhibition of PLCγ/PKC-induced mTOR activation impairs IL-7-mediated B cell development. PLCγ1/PLCγ2 double-deficient B cell progenitors have reduced expression of genes related to B cell lineage, IL-7 signaling, and cell cycle. Thus, IL-7 receptor controls early B lymphopoiesis through activation of mTOR via PLCγ/DAG/PKC signaling, not via Akt/Rheb signaling.

Original language	English (US)
Article number	1457
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-01388-5
State	Published - Dec 1 2017

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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Yu, M., Chen, Y., Zeng, H., Zheng, Y., Fu, G., Zhu, W., Broeckel, U., Aggarwal, P., Turner, A., Neale, G., Guy, C., Zhu, N., Chi, H., Wen, R., & Wang, D. (2017). PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development. Nature communications, 8(1), [1457]. https://doi.org/10.1038/s41467-017-01388-5

PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development. / Yu, Mei; Chen, Yuhong; Zeng, Hu; Zheng, Yongwei; Fu, Guoping; Zhu, Wen; Broeckel, Ulrich; Aggarwal, Praful; Turner, Amy; Neale, Geoffrey; Guy, Cliff; Zhu, Nan; Chi, Hongbo; Wen, Renren; Wang, Demin.

In: Nature communications, Vol. 8, No. 1, 1457, 01.12.2017.

Research output: Contribution to journal › Article

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abstract = "The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCγ signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCγ1/PLCγ2 double deficiency in mice blocks early B cell development at the pre-pro-B cell stage and renders B cell progenitors unresponsive to IL-7. PLCγ pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCγ pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis. Inhibition of PLCγ/PKC-induced mTOR activation impairs IL-7-mediated B cell development. PLCγ1/PLCγ2 double-deficient B cell progenitors have reduced expression of genes related to B cell lineage, IL-7 signaling, and cell cycle. Thus, IL-7 receptor controls early B lymphopoiesis through activation of mTOR via PLCγ/DAG/PKC signaling, not via Akt/Rheb signaling.",

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