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Publication : A recurrent clonotype in the spontaneous anti-IgG2a rheumatoid factor response of lpr/lpr mice.

First Author  Hande S Year  1996
Journal  J Immunol Volume  156
Issue  5 Pages  1856-64
PubMed ID  8596037 Mgi Jnum  J:31454
Mgi Id  MGI:78962 Doi  10.4049/jimmunol.156.5.1856
Citation  Hande S, et al. (1996) A recurrent clonotype in the spontaneous anti-IgG2a rheumatoid factor response of lpr/lpr mice. J Immunol 156(5):1856-64
abstractText  We generated mice transgenic for a V-H gene that partially encodes an anti-IgG2a rheumatoid factor, Such transgenic V- H 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 Ipr/Ipr 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 V-H, Surprisingly, however, most of the mice yielded multiple anti-IgG2a hybridomas that expressed V, genes comprised of a single V-H gene segment, D regions with highly homologous 5' ends encoding CDR3 regions of identical length, and the J(H)4 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 V-H 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 Ipr/Ipr littermate and from MRL Ipr/Ipr mice, These data contrast with the previous findings of others that while the spontaneous rheumatoid factor response of Ipr/Ipr mice was oligoclonal, recurrent clonotypes were not apparent, and the V-H and V kappa s encoding these rheumatoid factors contained a high frequency of somatic mutation whose distribution and type were indicative of Ag-driven selection.
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