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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1991-9-27
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pubmed:abstractText |
To determine the genetic origins of lupus auto-antibodies, we analyzed the relationship between VH gene usage and auto-Ag-binding properties of 352 B cell hybridomas derived from MRL-lpr/lpr mice. The hybridomas were derived from neonatal, 1-month-old, 3-month-old, and 6-month-old mice. The experimental strategy provided that the hybridomas were monoclonal at initial evaluation, so the Ag binding and V gene frequencies of the entire population could be determined. Initially, 1032 Ig-producing hybridomas were evaluated for binding to six Ag; VH gene family use was determined in 119 anti-DNA and anti-rabbit thymus extract (RTE) antibodies (autoantibodies) and in 233 age-matched Ig that did not bind to any of the six Ag (nonbinders). Neonatal B cells, including cross-reactive IgM autoantibodies and nonbinder IgM, used relatively 3' VH genes. The majority of B cells in adult mice used VH genes of the J558 family. Although J558 use was significantly higher among the autoantibodies (anti-DNA and anti-RTE) than among the nonbinder Ig, this difference was due to a higher frequency of J558 use by 1-month-old mice. At 3 months, J558 use by the nonbinder Ig increased to the same frequency of J558 use as in the autoantibody population. J558 use in both groups of antibodies exceeded a previously reported estimation of J558 expression in the functional B cell repertoire of young adult MRL-lpr/lpr mice. Several subgroups of antibodies that share properties with pathogenic Ig, including IgG, cross-reactive Ig, and anti-dsDNA autoantibodies, demonstrated a marked preferential expression of the J558 family. These results suggest that there is an age-related bias in the activation of B cells using J558 VH genes in MRL-lpr/lpr mice that is under the influence of a selective force distinct from, or in addition to, an ssDNA or RTE auto-Ag-driven response.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Antinuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantibodies,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Isotypes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
147
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1504-11
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:1908876-Animals,
pubmed-meshheading:1908876-Antibodies, Antinuclear,
pubmed-meshheading:1908876-Autoantibodies,
pubmed-meshheading:1908876-B-Lymphocytes,
pubmed-meshheading:1908876-Female,
pubmed-meshheading:1908876-Genes, Immunoglobulin,
pubmed-meshheading:1908876-Immunoglobulin Heavy Chains,
pubmed-meshheading:1908876-Immunoglobulin Isotypes,
pubmed-meshheading:1908876-Immunoglobulin Variable Region,
pubmed-meshheading:1908876-Lupus Erythematosus, Systemic,
pubmed-meshheading:1908876-Lymphocyte Activation,
pubmed-meshheading:1908876-Mice,
pubmed-meshheading:1908876-Rabbits,
pubmed-meshheading:1908876-Thymus Gland
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pubmed:year |
1991
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pubmed:articleTitle |
VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies.
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pubmed:affiliation |
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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