| Increased targeting of donor switch region and IgE in Sgamma1-deficient B cells. | |
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MedLine Citation:
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PMID: 20511552 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Ab class switch recombination involves a recombination between two repetitive DNA sequences known as switch (S) regions that vary in length, content, and density of the repeats. Abs expressed by B cells are diversified by somatic hypermutation and class switch recombination. Both class switch recombination and somatic hypermutation are initiated by activation-induced cytidine deaminase (AID), which preferentially recognizes certain hot spots that are far more enriched in the S regions. We found that removal of the largest S region, Sgamma1 (10 kb), in mice can result in the accumulation of mutations and short-range intra-S recombination in the donor Smu region. Furthermore, elevated levels of IgE were detected in trinitrophenol-OVA-immunized mice and in anti-CD40 plus IL-4-stimulated B cells in vitro. We propose that AID availability and targeting in part might be regulated by its DNA substrate. Thus, prominently transcribed S regions, such as Sgamma1, might provide a sufficient sink for AID protein to titrate away AID from other accessible sites within or outside the Ig locus. |
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Authors:
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Shahram Misaghi; Christopher S Garris; Yonglian Sun; Allen Nguyen; Juan Zhang; Andrew Sebrell; Kate Senger; Donghong Yan; Maria N Lorenzo; Sherry Heldens; Wyne P Lee; Min Xu; Jiansheng Wu; Laura DeForge; Tao Sai; Vishva M Dixit; Ali A Zarrin |
Publication Detail:
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Type: Journal Article Date: 2010-05-28 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-06-21 Completed Date: 2010-09-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 166-73 Citation Subset: AIM; IM |
Affiliation:
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Department of Physiological Chemistry, Genentech, San Francisco, CA 94080, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocyte Subsets / immunology*, metabolism* Cells, Cultured Gene Deletion* Gene Targeting* / methods Humans Immunoglobulin Class Switching / genetics* Immunoglobulin E / genetics, metabolism* Immunoglobulin Isotypes / genetics Immunoglobulin Switch Region / genetics* Mice Mice, Inbred C57BL Mice, Mutant Strains Recombination, Genetic / immunology Somatic Hypermutation, Immunoglobulin |
| Chemical | |
Reg. No./Substance:
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0/Immunoglobulin Isotypes; 37341-29-0/Immunoglobulin E |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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