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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., Benhamou, D., Riess, D., Blumenberg, L., Snetkova, V., Hines, M.J., Chakraborty, T., Bajwa, S., Jensen, K., Chong, M.M.W., Getu, L., Silverman, G.J., Blelloch, R., Littman, D.R., Calado, D., Melamed, D., Skok, J.A., 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 |
| 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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