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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
1999-8-19
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pubmed:abstractText |
During maturation of the immune response, IgM+ B cells switch to expression of one of the downstream isotypes (IgG, A or E). This class switching occurs by region-specific recombination within the IgH locus through an unknown mechanism. A lack of switch recombination in mice deficient in components of the DNA-dependent protein kinase (DNA-PK)-Ku complex has pointed to a role for non-homologous end joining. Here we characterize a switching defect in mice lacking a protein involved in DNA mismatch recognition. Mice deficient in Msh2 give diminished IgG (but not IgM) responses following challenge with both T cell-dependent and T cell-independent antigens. This appears to reflect a B cell-intrinsic defect since B cells from Msh2-deficient mice also exhibit impaired switching (but not blasting or proliferation) on in vitro culture with lipopolysaccharide. Furthermore, those switches that do occur in Msh2-deficient B cells reveal a shift in the distribution of recombination sites used: the breakpoints are more likely to occur in consensus motifs. These results, which intriguingly parallel the effects of Msh2 deficiency on hypermutation, suggest a role for Msh2 in the mechanics of class-switch recombination.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-10050672,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-1420357,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-7628020,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-7851796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8441648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8444838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8460148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8787624,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8834495,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8849883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-8885865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9018043,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9202128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9224606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9256462,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9343441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9368617,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9379005,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9501985,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9545251,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9607915,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9618520,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9625768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9634476,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9671757,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9697842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9697843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9707605,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9881975,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9881976,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10369687-9927509
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, T-Independent,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ficoll,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin A,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Msh2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/MutS Homolog 2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0261-4189
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3484-90
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:10369687-Animals,
pubmed-meshheading:10369687-Antigens, T-Independent,
pubmed-meshheading:10369687-B-Lymphocytes,
pubmed-meshheading:10369687-Base Pair Mismatch,
pubmed-meshheading:10369687-Base Sequence,
pubmed-meshheading:10369687-Cells, Cultured,
pubmed-meshheading:10369687-DNA Repair,
pubmed-meshheading:10369687-DNA-Binding Proteins,
pubmed-meshheading:10369687-Ficoll,
pubmed-meshheading:10369687-Immunoglobulin A,
pubmed-meshheading:10369687-Immunoglobulin Class Switching,
pubmed-meshheading:10369687-Immunoglobulin G,
pubmed-meshheading:10369687-Immunoglobulin M,
pubmed-meshheading:10369687-Lipopolysaccharides,
pubmed-meshheading:10369687-Lymphocyte Activation,
pubmed-meshheading:10369687-Mice,
pubmed-meshheading:10369687-Mice, Knockout,
pubmed-meshheading:10369687-Molecular Sequence Data,
pubmed-meshheading:10369687-MutS Homolog 2 Protein,
pubmed-meshheading:10369687-Mutagenesis,
pubmed-meshheading:10369687-Mutation,
pubmed-meshheading:10369687-Peyer's Patches,
pubmed-meshheading:10369687-Proto-Oncogene Proteins,
pubmed-meshheading:10369687-Recombination, Genetic
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pubmed:year |
1999
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pubmed:articleTitle |
Deficiency in Msh2 affects the efficiency and local sequence specificity of immunoglobulin class-switch recombination: parallels with somatic hypermutation.
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pubmed:affiliation |
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK.
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pubmed:publicationType |
Journal Article
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