IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development
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Open Access
- 27 June 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (14) , 1703-1708
- https://doi.org/10.1101/gad.1104803
Abstract
B-lymphocyte development involves sequential DNA rearrangements of immunoglobulin (Ig) heavy (μ) and light (κ, λ) chain loci and is dependent on transient expression of μ 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.Keywords
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