Skip to main content
eScholarship
Open Access Publications from the University of California

miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation

  • Author(s): Coffre, M
  • Benhamou, D
  • Rieß, D
  • Blumenberg, L
  • Snetkova, V
  • Hines, MJ
  • Chakraborty, T
  • Bajwa, S
  • Jensen, K
  • Chong, MMW
  • Getu, L
  • Silverman, GJ
  • Blelloch, R
  • Littman, DR
  • Calado, D
  • Melamed, D
  • Skok, JA
  • Rajewsky, K
  • Koralov, SB
  • et al.

Published Web Location

http://www.cell.com/cell-reports/fulltext/S2211-1247(16)31527-3
No data is associated with this publication.
Abstract

© 2016 The Author(s) 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.

Item not freely available? Link broken?
Report a problem accessing this item