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The pre-B-cell receptor induces silencing of VpreB and lambda5 transcription. | LitMetric

AI Article Synopsis

  • The pre-B-cell receptor (pre-BCR) plays a critical role in promoting the growth of pre-BII cells and is also involved in downregulating surrogate light chain (SLC) genes, which limits this cell expansion.
  • * As B cells transition from pre-BI to large pre-BII stages, the lambda5 gene shows a shift from being expressed from both alleles to only one, indicating a controlled silencing process.
  • * Pre-BCR-deficient mice exhibit delayed downregulation of lambda5, confirming the receptor's necessity for proper gene silencing, and SLP-65 is identified as an important signaling molecule in this regulation.*

Article Abstract

The pre-B-cell receptor (pre-BCR), composed of Ig heavy and surrogate light chain (SLC), signals pre-BII-cell proliferative expansion. We have investigated whether the pre-BCR also signals downregulation of the SLC genes (VpreB and lambda5), thereby limiting this expansion. We demonstrate that, as BM cells progress from the pre-BI to large pre-BII-cell stage, there is a shift from bi- to mono-allelic lambda5 transcription, while the second allele is silenced in small pre-BII cells. A VpreB1-promoter-driven transgene shows the same pattern, therefore suggesting that VpreB1 is similarly regulated and thereby defines the promoter as a target for transcriptional silencing. Analyses of pre-BCR-deficient mice show a temporal delay in lambda5 downregulation, thereby demonstrating that the pre-BCR is essential for monoallelic silencing at the large pre-BII-cell stage. Our data also suggest that SLP-65 is one of the signaling components important for this process. Furthermore, the VpreB1/lambda5 alleles undergo dynamic changes with respect to nuclear positioning and heterochromatin association, thereby providing a possible mechanism for their transcriptional silencing.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1283949PMC
http://dx.doi.org/10.1038/sj.emboj.7600850DOI Listing

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