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Publication : IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development.

First Author  Lu R Year  2003
Journal  Genes Dev Volume  17
Issue  14 Pages  1703-8
PubMed ID  12832394 Mgi Jnum  J:84577
Mgi Id  MGI:2668304 Doi  10.1101/gad.1104803
Citation  Lu R, et al. (2003) IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development. Genes Dev 17(14):1703-8
abstractText  B-lymphocyte development involves sequential DNA rearrangements of immunoglobulin (Ig) heavy (mu) and light (kappa, lambda) chain loci and is dependent on transient expression of mu containing pre-antigen receptor complexes (pre-BCR). To date, genetic analysis has not identified transcription factors that coordinate the pre-B-to-B transition. We demonstrate that the related interferon regulatory factors IRF-4 (Pip) and IRF-8 (ICSBP) are required for Ig light but not heavy-chain gene rearrangement. In the absence of these transcription factors, B-cell development is arrested at the cycling pre-B-cell stage and the mutant cells fail to down-regulate the pre-BCR. On the basis of molecular analysis, we propose that IRF-4,8 function as a genetic switch to down-regulate surrogate light-chain gene expression and induce conventional light-chain gene transcription and rearrangement.
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