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

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Item Type:Article
Title:miRNAs are essential for the regulation of the PI3K/AKT/FOXO pathway and receptor editing during B cell maturation
Creators Name:Coffre, M. and Benhamou, D. and Riess, D. and Blumenberg, L. and Snetkova, V. and Hines, M.J. and Chakraborty, T. and Bajwa, S. and Jensen, K. and Chong, M.M.W. and Getu, L. and Silverman, G.J. and Blelloch, R. and Littman, D.R. and Calado, D. and Melamed, D. and Skok, J.A. and Rajewsky, K. and Koralov, S.B.
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.
Keywords:B Lymphocytes, miRNA, Dicer, Drosha, DGCR8, RAG, PTEN, PI3K/AKT, B Cell Development, Receptor Editing, Animals, Mice
Source:Cell Reports
ISSN:2211-1247
Publisher:Cell Press / Elsevier (U.S.A.)
Volume:17
Number:9
Page Range:2271-2285
Date:22 November 2016
Official Publication:https://doi.org/10.1016/j.celrep.2016.11.006
PubMed:View item in PubMed

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