Proc. Natl. Acad. Sci. U.S.A. 2009 Jan
Amin RH, Cado D, Nolla H, Huang D, Shinton SA, Zhou Y, Hardy RR, Schlissel MS
Abstract
Allelic exclusion of Ig gene expression is necessary to limit the number of functional receptors to one per B cell. The mechanism underlying allelic exclusion is unknown. Because germline transcription of Ig and TCR loci is tightly correlated with rearrangement, we created two novel knock-in mice that report transcriptional activity of the Jkappa germline promoters in the Igkappa locus. Analysis of these mice revealed that germline transcription is biallelic and occurs in all pre-B cells. Moreov
...[more]er, we found that the two germline promoters in this region are not equivalent but that the distal promoter accounts for the vast majority of observed germline transcript in pre-B cells while the activity of the proximal promoter increases later in development. Allelic exclusion of the Igkappa locus thus occurs at the level of rearrangement, but not germline transcription.
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Mesh Headings:
Alleles, Animals, B-Lymphocytes, Gene Knock-In Techniques, Gene Rearrangement, Humans, Immunoglobulin kappa-Chains, Mice, Mice, Transgenic, Precursor Cells, B-Lymphoid, Promoter Regions, Genetic, Transcription, Genetic