Dicer ablation affects antibody diversity and cell survival in the B lymphocyte lineage - PubMed (original) (raw)

. 2008 Mar 7;132(5):860-74.

doi: 10.1016/j.cell.2008.02.020.

Affiliations

• PMID: 18329371
• DOI: 10.1016/j.cell.2008.02.020

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

Sergei B Koralov et al. Cell. 2008.

Free article

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.

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Comment in

• MicroRNAs and lymphocyte homeostasis: dangerous eggs in a single basket.
  Mérino D, Bouillet P. Mérino D, et al. Immunol Cell Biol. 2008 Jul;86(5):387-8. doi: 10.1038/icb.2008.33. Epub 2008 May 20. Immunol Cell Biol. 2008. PMID: 18490933 No abstract available.

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