IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development (original) (raw)
- Runqing Lu,
- Kay L. Medina,
- David W. Lancki, and
- Harinder Singh1
- Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois 60637, USA
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.
Footnotes
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1104803.
↵1 Corresponding author. E-MAIL hsingh{at}midway.uchicago.edu; FAX (773) 702-3611.
- Accepted May 23, 2003.
- Received April 17, 2003.
Cold Spring Harbor Laboratory Press