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

Cell. 2008 Mar 7;132(5):860-74. doi: 10.1016/j.cell.2008.02.020.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3' Untranslated Regions / chemistry
  • 3' Untranslated Regions / metabolism
  • Animals
  • Antibody Diversity*
  • B-Lymphocytes / cytology*
  • Blotting, Northern
  • Cell Survival*
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism*
  • Endoribonucleases / genetics*
  • Endoribonucleases / metabolism*
  • Gene Expression Profiling
  • Gene Rearrangement, B-Lymphocyte
  • Immunoglobulins / genetics
  • Mice
  • Mice, Knockout
  • MicroRNAs / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonuclease III
  • Specific Pathogen-Free Organisms


  • 3' Untranslated Regions
  • Immunoglobulins
  • MicroRNAs
  • Endoribonucleases
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases