| Expression of AID transgene is regulated in activated B cells but not in resting B cells and kidney. | |
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MedLine Citation:
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PMID: 18067961 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced DNA cytidine deaminase (AID) is required for somatic hypermutation (SHM) and efficient class switch recombination (CSR) of immunoglobulin (Ig) genes. We created AID-transgenic mice that express AID ubiquitously under the control of a beta-actin promoter. When crossed with AID-/- mice, the AID-transgenic,AID-/- mice carried out SHM and CSR, showing that the AID transgenes were functional. However, the frequencies of SHM in V- and switch-regions, and CSR were reduced compared to those in a wild type AID background. Several criteria suggested that the inefficiency of SHM was due to reduced AID activity, rather than lack of recruiting error-prone DNA repair. High levels of AID mRNA were produced in resting B cells and kidney, cells that do not express AID in wild type mice. Compared with these cells, activated B cells expressed about an order of magnitude less AID mRNA suggesting that there may be a post-transcriptional mechanism that regulates AID mRNA levels in professional AID producers but not other cells. The AID protein expressed in resting B cells and kidney was phosphorylated at serine-38. Despite this modification, known to enhance AID activity, resting B cells did not undergo SHM. Apparently, the large amounts of AID in resting B cells are not targeted to Ig genes in vivo, in contrast to findings in vitro. |
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Authors:
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Hong Ming Shen; Grazyna Bozek; Carl A Pinkert; Kevin McBride; Lili Wang; Amy Kenter; Ursula Storb |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-12-11 |
Journal Detail:
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Title: Molecular immunology Volume: 45 ISSN: 0161-5890 ISO Abbreviation: Mol. Immunol. Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-02-18 Completed Date: 2008-04-24 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 7905289 Medline TA: Mol Immunol Country: England |
Other Details:
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Languages: eng Pagination: 1883-92 Citation Subset: IM |
Affiliation:
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Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals B-Lymphocytes / cytology*, enzymology* Cytidine Deaminase / genetics* Flow Cytometry Gene Expression Regulation, Enzymologic* Immunoglobulin Class Switching / immunology Kidney / enzymology* Lymphocyte Activation / immunology* Mice Mice, Inbred C57BL Mutation / genetics Phosphorylation Proliferating Cell Nuclear Antigen / metabolism RNA, Messenger / genetics, metabolism Serine / metabolism Somatic Hypermutation, Immunoglobulin / immunology Transgenes* |
| Grant Support | |
ID/Acronym/Agency:
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AI052400/AI/NIAID NIH HHS; AI053130/AI/NIAID NIH HHS; R01 AI047380-07/AI/NIAID NIH HHS; R01 AI052400-05A2/AI/NIAID NIH HHS; R01 AI053130-05/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Proliferating Cell Nuclear Antigen; 0/RNA, Messenger; 56-45-1/Serine; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
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