Journal article

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

Maryaline Coffre, David Benhamou, David Riess, Lili Blumenberg, Valentina Snetkova, Marcus J Hines, Tirtha Chakraborty, Sofia Bajwa, Kari Jensen, Mark MW Chong, Lelise Getu, Gregg J Silverman, Robert Blelloch, Dan R Littman, Dinis Calado, Doron Melamed, Jane A Skok, Klaus Rajewsky, Sergei B Koralov

CELL REPORTS | CELL PRESS | Published : 2016

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 immunoglobuli..

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University of Melbourne Researchers

Grants

Awarded by NIAID


Awarded by NIH


Awarded by European Research Council


Awarded by Israel Science Foundation


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by Cancer Research UK


Awarded by Medical Research Council


Awarded by The Francis Crick Institute


Funding Acknowledgements

We thank Dr. Pelanda for sharing the AKT/pAKT staining protocol with us. We thank Pedro Rocha for his help with ImmunoFISH analysis. We thank NYU Medical Center Cytometry and Cell Sorting Core for assistance. We thank all members of the Koralov lab for regular discussions of the presented results. We apologize to authors whose work we could not cite due to space constraints. Koralov lab is grateful for support from NIAID (R21AI110830-01), Beckman Foundation, and Ralph S. French Charitable Trust. K.R. was funded by NIH (1R01AI064345-01) and the European Research Council (Advanced Grant 268921) and D.M. lab was funded by The Israel Science Foundation (1408/13).