Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage

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Item Type:	Article
Title:	Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage
Creators Name:	Koralov, S.B., Muljo, S.A., Galler, G.R., Krek, A., Chakraborty, T., Kanellopoulou, C., Jensen, K., Cobb, B.S., Merkenschlager, M., Rajewsky, N. and Rajewsky, K.
Abstract:	To explore the role of Dicer-dependent control mechanisms in B lymphocyte development, we ablated this enzyme in early B cell progenitors. This resulted in a developmental block at the pro- to pre-B cell transition. Gene-expression profiling revealed a miR-17 approximately 92 signature in the 3'UTRs of genes upregulated in Dicer-deficient pro-B cells; a top miR-17 approximately 92 target, the proapoptotic molecule Bim, was highly upregulated. Accordingly, B cell development could be partially rescued by ablation of Bim or transgenic expression of the prosurvival protein Bcl-2. This allowed us to assess the impact of Dicer deficiency on the V(D)J recombination program in developing B cells. We found intact Ig gene rearrangements in immunoglobulin heavy (IgH) and kappa chain loci, but increased sterile transcription and usage of D(H) elements of the DSP family in IgH, and increased N sequence addition in Igkappa due to deregulated transcription of the terminal deoxynucleotidyl transferase gene.
Keywords:	RNA, DEVBIO
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	132
Number:	5
Page Range:	860-874
Date:	7 March 2008
Official Publication:	https://doi.org/10.1016/j.cell.2008.02.020
PubMed:	View item in PubMed

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