miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation
Year: 2016
Type: article
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.
Source: Cell Reports
Authors: Maryaline Coffre, David Benhamou, David Rieß, Lili Blumenberg, Valentina Snetkova, Marcus J. Hines, Tirtha Chakraborty, Sofia Bajwa, Kari Jensen, Mark M.W. Chong, Lelise Getu, Gregg J. Silverman, Robert Blelloch, Dan R. Littman, Dinis Calado, Doron Melamed, Jane A. Skok, Klaus Rajewsky, Sergei B. Koralov
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,620
Funders: Arnold and Mabel Beckman Foundation, Francis Crick Institute, Cancer Research UK, Israel Science Foundation, National Institutes of Health, Medical Research Council, European Research Council, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, FP7 Ideas: European Research Council
Awards: Modeling lymphoma pathogenesis in mice - from basic mechanisms to pre-clinical models, Non-coding RNAs in B lymphocyte development and function, Medical Scientist Research Service Award, G5078730493, G5097785644, G6888785958, Role of RNA silencing in B cell development and function, G8900576967
OpenAlex ID: W2556845933