miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation
Autor/innen
- 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
Quellenangabe
- Cell Rep 17 (9): 2271-2285
Zusammenfassung
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.