Faculty Collaboration Database

PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development. Nat Commun 2017 Nov 13;8(1):1457

Date

11/15/2017

Pubmed ID

29133930

Pubmed Central ID

PMC5684131

DOI

10.1038/s41467-017-01388-5

Scopus ID

2-s2.0-85034212045 (requires institutional sign-in at Scopus site)   26 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.

Author List

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

Authors

Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of Wisconsin
Amy Turner Research Scientist I in the Pediatrics department at Medical College of Wisconsin
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Nan Zhu PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Female
Interleukin-7
Lymphopoiesis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Phospholipase C gamma
Precursor Cells, B-Lymphoid
STAT5 Transcription Factor
Signal Transduction
TOR Serine-Threonine Kinases