Journal
GENES & DEVELOPMENT
Volume 17, Issue 14, Pages 1703-1708Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1104803
Keywords
IRF-4; IRF-8; Ets-IRF complexes; lymphocyte development
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B-lymphocyte development involves sequential DNA rearrangements of immunoglobulin (Ig) heavy (la) and light (kappa, lambda) chain loci and is dependent on transient expression of p 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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