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Publication : Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b cells contributes to the allelic exclusion of light-chain expression.

First Author  Liang HE Year  2004
Journal  Cell Volume  118
Issue  1 Pages  19-29
PubMed ID  15242641 Mgi Jnum  J:91295
Mgi Id  MGI:3046394 Doi  10.1016/j.cell.2004.06.019
Citation  Liang HE, et al. (2004) Variegated transcriptional activation of the immunoglobulin kappa locus in pre-b cells contributes to the allelic exclusion of light-chain expression. Cell 118(1):19-29
abstractText  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.
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