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| Subject Categories: Chromatin & Transcription | Immunology |
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| The EMBO Journal
(2005) 24, 3895–3905, doi:10.1038/sj.emboj.7600850 Published online 10 November 2005 |
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The pre-B-cell receptor induces silencing of VpreB and  5 transcription |
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| Mathew J Parker1, Steve Licence1, Lena Erlandsson1, Gunther R Galler2, Lyubomira Chakalova3, Cameron S Osborne3, Geoff Morgan4, Peter Fraser3, Hassan Jumaa5, Thomas H Winkler2, Jane Skok6 and Inga-Lill Mårtensson1 |
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1 Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, UK 2 Hematopoiesis Unit, Nikolaus-Fiebiger-Center, Erlangen, Germany 3 Laboratory of Chromatin and Gene Expression, The Babraham Institute, Cambridge, UK 4 Flow Cytometry Facility, The Babraham Institute, Cambridge, UK 5 Institute for Biology III, Max-Planck-Institute for Immunobiology, Freiburg, Germany 6 Department of Immunology and Molecular Pathology, UCL, London, UK To whom correspondence should be addressed Inga-Lill Mårtensson, Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, UK. Tel.: +44 1223 496469; Fax: +44 1223 496023; E-mail: lill.martensson@bbsrc.ac.uk Received 29 April 2005; Accepted 6 October 2005; Published online 10 November 2005. |
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| Abstract |
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| 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 5), 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 5 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 5 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 VpreB1/5 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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| Keywords: B-cell development, heterochromatin, pre-B-cell receptor, SLP-65, surrogate light chain |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSNature Immunology News and Views (01 Dec 2004) How pre-B cells know when they have it right Nature Immunology News and Views (01 Sep 2003) RESEARCHJournal of Investigative Dermatology Letter Transcription of productive and nonproductive VDJ-recombined alleles after IgH allelic exclusion The EMBO Journal Article (03 Oct 2007) |
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