IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development.
B-lymphocyte development involves sequential DNA rearrangements of immunoglobulin (Ig) heavy (mu) and light (kappa, lambda) chain loci and is dependent on transient expression of mu 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.
Lu
Runqing
R
Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL 60637, USA.
Medina
Kay L
KL
Lancki
David W
DW
Singh
Harinder
H
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4
D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; D000099218:Interferon Regulatory Factor-4