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

R Lu, KL Medina, DW Lancki, H Singh - Genes & development, 2003 - genesdev.cshlp.org
R Lu, KL Medina, DW Lancki, H Singh
Genes & development, 2003genesdev.cshlp.org
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 …
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.
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