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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-4-15
pubmed:abstractText
We generated mice transgenic for a VH gene that partially encodes an anti-IgG2a rheumatoid factor. Such transgenic VH genes recombine at a low frequency with the endogenous Igh locus in mice, giving rise to a small number of B cells that express heavy chains partially encoded by the transgene. The transgenes were crossed onto an lpr/lpr background, and hybridomas were generated from the resulting mice at 3 to 6 mo of age. Analysis of the anti-IgG2a- producing hybridomas obtained revealed that none expressed the transgenic VH. Surprisingly, however, most of the mice yielded multiple anti-IgG2a hybridomas that expressed VH genes comprised of a single VH gene segment, D regions with highly homologous 5' ends encoding CDR3 regions of identical length, and the JH4 segment. Expressed light chain diversity among these hybridomas was also highly restricted; most expressed a single V kappa gene segment. All of the hybridomas expressed members of the V kappa 19/28 family. Many of the VH genes contained a low frequency of somatic mutation. The recurrence of this family of V regions is not due to an indirect transgene effect or to effects of the genetic background used to construct the mice, as hybridomas expressing the predominant V gene segment combination were also isolated from a transgene-negative lpr/lpr littermate and from MRL lpr/lpr mice. These data contrast with the previous findings of others that while the spontaneous rheumatoid factor response of lpr/lpr mice was oligoclonal, recurrent clonotypes were not apparent, and the VH and V kappas encoding these rheumatoid factors contained a high frequency of somatic mutation whose distribution and type were indicative of Ag-driven selection.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
156
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1856-64
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8596037-Animals, pubmed-meshheading:8596037-Antibodies, Anti-Idiotypic, pubmed-meshheading:8596037-Base Sequence, pubmed-meshheading:8596037-Clone Cells, pubmed-meshheading:8596037-Female, pubmed-meshheading:8596037-Genes, Immunoglobulin, pubmed-meshheading:8596037-Immunoglobulin G, pubmed-meshheading:8596037-Immunoglobulin Heavy Chains, pubmed-meshheading:8596037-Immunoglobulin Variable Region, pubmed-meshheading:8596037-Male, pubmed-meshheading:8596037-Mice, pubmed-meshheading:8596037-Mice, Inbred C3H, pubmed-meshheading:8596037-Mice, Inbred C57BL, pubmed-meshheading:8596037-Mice, Mutant Strains, pubmed-meshheading:8596037-Mice, Transgenic, pubmed-meshheading:8596037-Molecular Sequence Data, pubmed-meshheading:8596037-Rheumatoid Factor, pubmed-meshheading:8596037-Spleen
pubmed:year
1996
pubmed:articleTitle
A recurrent clonotype in the spontaneous anti-IgG2a rheumatoid factor response of lpr/lpr mice.
pubmed:affiliation
Department of Microbiology and Immunology, Thomas Jefferson Medical College, Philadelphia, PA 19017, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.