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

Item Type:Article
Title:Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage
Creators Name:Koralov, S.B. and Muljo, S.A. and Galler, G.R. and Krek, A. and Chakraborty, T. and Kanellopoulou, C. and Jensen, K. and Cobb, B.S. and Merkenschlager, M. and 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
Publisher:Cell Press
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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