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Publication : The anti-La response of a single MRL/Mp-lpr/lpr mouse: specificity for DNA and VH gene usage.

First Author  Bloom DD Year  1994
Journal  Eur J Immunol Volume  24
Issue  6 Pages  1332-8
PubMed ID  8206093 Mgi Jnum  J:18907
Mgi Id  MGI:67127 Doi  10.1002/eji.1830240614
Citation  Bloom DD, et al. (1994) The anti-La response of a single MRL/Mp-lpr/lpr mouse: specificity for DNA and VH gene usage. Eur J Immunol 24(6):1332-8
abstractText  Autoantibodies to ribonucleoproteins (RNP) occur prominently in human systemic lupus erythematosus and murine lupus models. In previous studies we demonstrated a relationship in MRL/Mp-lpr/lpr (MRL/lpr) mice between antibodies to Sm, an RNP autoantigen, and antibodies to DNA. Thus, many anti-Sm monoclonals bound DNA and expressed the same V region genes as anti-DNA. In addition, many had multiple VHCDR3 Arg residues suggestive of selection by DNA, and some had somatic mutations suggesting selection for mutant B cells by DNA. To determine whether autoantibodies to other RNP antigens are also associated with the anti-DNA response, we have analyzed the response to the La RNP. Six anti-La B cell hybridomas were generated from a single MRL/lpr mouse. Southern blot analysis of Ig V gene rearrangements and V gene sequences indicated two clonally related pairs, suggesting an oligoclonal response. Antibodies from all six hybridomas bound single-stranded DNA, while antibodies from five hybridomas bound double-stranded DNA. Two hybridomas expressed a VH7183 gene which is used by members of two previously reported anti-DNA clones and two anti-Sm/DNA clones of MRL/lpr origin. These data demonstrate an association between the anti-La and anti-DNA responses in MRL/lpr mice, suggesting that cross-reactive anti-RNP and anti-DNA responses are a general feature of autoimmunity in this lupus model.
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