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

Runqing Lu, Kay L. Medina, David W. Lancki, Harinder Singh

Research output: Contribution to journalArticle

184 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1703-1708
Number of pages6
JournalGenes and Development
Volume17
Issue number14
DOIs
StatePublished - Jul 15 2003

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Keywords

  • Ets-IRF complexes
  • IRF-4
  • IRF-8
  • Lymphocyte development

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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