| First Author | Yu M | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Issue | 1 | Pages | 1457 |
| PubMed ID | 29133930 | Mgi Jnum | J:256303 |
| Mgi Id | MGI:6106339 | Doi | 10.1038/s41467-017-01388-5 |
| Citation | Yu M, et al. (2017) PLCgamma-dependent mTOR signalling controls IL-7-mediated early B cell development. Nat Commun 8(1):1457 |
| abstractText | The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLCgamma signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLCgamma1/PLCgamma2 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. PLCgamma pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLCgamma pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis. Inhibition of PLCgamma/PKC-induced mTOR activation impairs IL-7-mediated B cell development. PLCgamma1/PLCgamma2 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 PLCgamma/DAG/PKC signaling, not via Akt/Rheb signaling. |
