Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 2, Pages 522-527Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0808895106
Keywords
allelic exclusion; knock-in mouse
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Funding
- National Institutes of Health [R01 HL48702]
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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 J kappa germline promoters in the Ig kappa locus. Analysis of these mice revealed that germline transcription is biallelic and occurs in all pre-B cells. Moreover, 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 Ig kappa locus thus occurs at the level of rearrangement, but not germline transcription.
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