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

The precise molecular mechanism underlying the regulation of early B cell lymphopoiesis is unclear. The PLC gamma signaling pathway is critical for antigen receptor-mediated lymphocyte activation, but its function in cytokine signaling is unknown. Here we show that PLC gamma 1/PLC gamma 2 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. PLC gamma pathway inhibition blocks IL-7-induced activation of mTOR, but not Stat5. The PLC gamma pathway activates mTOR through the DAG/PKC signaling branch, independent of the conventional Akt/TSC/Rheb signaling axis. Inhibition of PLC gamma/PKC-induced mTOR activation impairs IL-7-mediated B cell development. PLC gamma 1/PLC gamma 2 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 PLC gamma/DAG/PKC signaling, not via Akt/Rheb signaling.