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Dicer Ablation Affects Antibody Diversity and Cell Survival in the B Lymphocyte Lineage
Open accessAbstract
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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(2012) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Metadata
- Authors
- Koralov, S. B., Muljo, S. A., Galler, G. R., Krek, A., Chakraborty, T., Kanellopoulou, C., Jensen, K., Cobb, B. S., Merkenschlager, M., Rajewsky, N., & Rajewsky, K.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 132
- Issue
- 5
- Pages
- 860-874
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1966427699
- Cited by
- 575
- References
- 5
- FWCI
- 24.35
- Type
- journal article
- Language
- en
- Open access
- hybrid
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