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

Author

Listed:
  • Mei Yu

    (Blood Research Institute, Blood Center of Wisconsin)

  • Yuhong Chen

    (Blood Research Institute, Blood Center of Wisconsin)

  • Hu Zeng

    (St. Jude Children’s Research Hospital)

  • Yongwei Zheng

    (Blood Research Institute, Blood Center of Wisconsin)

  • Guoping Fu

    (Blood Research Institute, Blood Center of Wisconsin)

  • Wen Zhu

    (Blood Research Institute, Blood Center of Wisconsin
    Interdisciplinary Program in Biomedical Sciences)

  • Ulrich Broeckel

    (Medical College of Wisconsin)

  • Praful Aggarwal

    (Medical College of Wisconsin)

  • Amy Turner

    (Medical College of Wisconsin)

  • Geoffrey Neale

    (Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children’s Research Hospital)

  • Cliff Guy

    (St. Jude Children’s Research Hospital)

  • Nan Zhu

    (Blood Research Institute, Blood Center of Wisconsin)

  • Hongbo Chi

    (St. Jude Children’s Research Hospital)

  • Renren Wen

    (Blood Research Institute, Blood Center of Wisconsin)

  • Demin Wang

    (Blood Research Institute, Blood Center of Wisconsin
    Fujian Normal University, Fuzhou
    Medical College of Wisconsin)

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.

Suggested Citation

  • 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, 2017. "PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development," Nature Communications, Nature, vol. 8(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01388-5
    DOI: 10.1038/s41467-017-01388-5
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    Cited by:

    1. Souleymane Abdoul-Azize & Rihab Hami & Gaetan Riou & Céline Derambure & Camille Charbonnier & Jean-Pierre Vannier & Monica L. Guzman & Pascale Schneider & Olivier Boyer, 2024. "Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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