Article
- The EMBO Journal (2005) 24, 3895 - 3905
- doi:10.1038/sj.emboj.7600850
Published online: 10 November 2005
Subject Categories:
The pre-B-cell receptor induces silencing of VpreB and 
5 transcription
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
- Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, UK
- Hematopoiesis Unit, Nikolaus-Fiebiger-Center, Erlangen, Germany
- Laboratory of Chromatin and Gene Expression, The Babraham Institute, Cambridge, UK
- Flow Cytometry Facility, The Babraham Institute, Cambridge, UK
- Institute for Biology III, Max-Planck-Institute for Immunobiology, Freiburg, Germany
- Department of Immunology and Molecular Pathology, UCL, London, UK
Correspondence to:
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
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 
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.
Keywords:
- B-cell development,
- heterochromatin,
- pre-B-cell receptor,
- SLP-65,
- surrogate light chain
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