PLCγ-dependent mTOR signalling controls IL-7-mediated early B cell development.
Nat Commun
; 8(1): 1457, 2017 11 13.
Article
in En
| MEDLINE
| ID: mdl-29133930
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Interleukin-7
/
Lymphopoiesis
/
Phospholipase C gamma
/
Precursor Cells, B-Lymphoid
/
TOR Serine-Threonine Kinases
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2017
Document type:
Article
Affiliation country:
United States