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

180 Citations (Scopus)

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

Fingerprint

Gene Rearrangement
Lymphocytes
Surrogate Immunoglobulin Light Chains
B-Lymphocytes
Transcription Factors
Down-Regulation
Immunoglobulin Light Chains
Light
Immunoglobulin Heavy Chains
Antigen Receptors
B-Lymphoid Precursor Cells
Immunoglobulins
Gene Expression
interferon regulatory factor-8

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development. / Lu, Runqing; Medina, Kay L.; Lancki, David W.; Singh, Harinder.

In: Genes and Development, Vol. 17, No. 14, 15.07.2003, p. 1703-1708.

Research output: Contribution to journalArticle

Lu, R, Medina, KL, Lancki, DW & Singh, H 2003, 'IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development', Genes and Development, vol. 17, no. 14, pp. 1703-1708. https://doi.org/10.1101/gad.1104803
Lu, Runqing ; Medina, Kay L. ; Lancki, David W. ; Singh, Harinder. / IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development. In: Genes and Development. 2003 ; Vol. 17, No. 14. pp. 1703-1708.
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