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miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation

Authors

  • M. Coffre
  • D. Benhamou
  • D. Riess
  • L. Blumenberg
  • V. Snetkova
  • M.J. Hines
  • T. Chakraborty
  • S. Bajwa
  • K. Jensen
  • M.M.W. Chong
  • L. Getu
  • G.J. Silverman
  • R. Blelloch
  • D.R. Littman
  • D. Calado
  • D. Melamed
  • J.A. Skok
  • K. Rajewsky
  • S.B. Koralov

Journal

  • Cell Reports

Citation

  • Cell Rep 17 (9): 2271-2285

Abstract

  • B cell development is a tightly regulated process dependent on sequential rearrangements of immunoglobulin loci that encode the antigen receptor. To elucidate the role of microRNAs (miRNAs) in the orchestration of B cell development, we ablated all miRNAs at the earliest stage of B cell development by conditionally targeting the enzymes critical for RNAi in early B cell precursors. Absence of any one of these enzymes led to a block at the pro- to pre-B cell transition due to increased apoptosis and a failure of pre-B cells to proliferate. Expression of a Bcl2 transgene allowed for partial rescue of B cell development, however, the majority of the rescued B cells had low surface immunoglobulin expression with evidence of ongoing light chain editing. Our analysis revealed that miRNAs are critical for the regulation of the PTEN-AKT-FOXO1 pathway that in turn controls Rag expression during B cell development.


DOI

doi:10.1016/j.celrep.2016.11.006