Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b cells contributes to the allelic exclusion of light-chain expression.
Regulated gene rearrangement is thought to underlie allelic exclusion, the observation that an individual B cell expresses only a single immunoglobulin molecule. Previous data has implicated transcriptional activation of rearranging loci in the regulation of their accessibility to the V(D)J recombinase. Using homologous recombination in ES cells, we have generated "knockin" mice which express a GFP cDNA from an unrearranged immunoglobulin kappa light-chain allele. Surprisingly, we find that only a small fraction of kappa alleles are highly transcribed in a population of pre-B cells, that such transcription is monoallelic, and that these highly transcribed alleles account for the vast majority of kappa light-chain gene rearrangement. These data lead us to suggest that probabilistic enhancer activation and allelic competition are part of the mechanism of kappa locus allelic exclusion and may be a general mechanism contributing to cellular differentiation during development.
Liang
Hong-Erh
HE
Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Hsu
Lih-Yun
LY
Cado
Dragana
D
Schlissel
Mark S
MS
D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000276:immunology; D019070:Cell Lineage; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic; D018628:Gene Dosage; D018507:Gene Expression Regulation, Developmental; D005787:Gene Frequency; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology; D005803:Genes, Immunoglobulin; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D006579:Heterozygote; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000276:immunology*; D015533:Transcriptional Activation
D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins