Biallelic, ubiquitous transcription from the distal germline Ig{kappa} locus promoter during B cell development

Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):522-7. doi: 10.1073/pnas.0808895106. Epub 2008 Dec 30.

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. 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 Igkappa locus thus occurs at the level of rearrangement, but not germline transcription.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alleles*
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Gene Knock-In Techniques
  • Gene Rearrangement
  • Humans
  • Immunoglobulin kappa-Chains / genetics*
  • Mice
  • Mice, Transgenic
  • Precursor Cells, B-Lymphoid / cytology
  • Precursor Cells, B-Lymphoid / immunology
  • Promoter Regions, Genetic*
  • Transcription, Genetic*

Substances

  • Immunoglobulin kappa-Chains