Expression of a highly conserved anti-DNA idiotype in normal and autoimmune mice.
The specificity and idiotypic relationships of a monoclonal anti-DNA antibody were investigated to evaluate genetic control in this autoantibody response. 6/0 is an IgG2a monoclonal anti-DNA derived by the fusion of spleen cells from an autoimmune MRL-lpr/lpr mouse and the cell line NS1. By an enzyme-linked immunosorbent assay (ELISA) for anti-DNA, 6/0 demonstrated preference for single-stranded DNA and bound deoxyribo- and ribohomopolymers of dissimilar base composition. The control of 6/0 expression was evaluated by idiotypic analysis using a rabbit anti-6/0 antiserum made specific by absorption with the BALB/c myelomas UPC 10 (IgG2a) and MOPC 21 (IgG1). The resulting preparation was fractionated by BALB/c IgG affinity columns to provide antibodies to idiotypic determinants essentially unique to 6/0 and those commonly expressed in sera. The commonly expressed 6/0 idiotype was found in sera of ten inbred strains of mice and was not exclusive to the autoimmune strains. MRL-lpr/lpr and A/J strain mice displayed idiotype levels almost fivefold greater than other strains, with 6/0 idiotype-bearing antibodies having serum concentrations as high as 1 mg/ml. Levels of the 6/0 idiotype, however, did not correlate with anti-DNA levels among the various strains. In addition to mice, the majority of individuals of three inbred rat strains showed detectable 6/0 idiotype in their sera. These results suggest that the 6/0 idiotype, although identified using a monoclonal anti-DNA antibody, represents a framework determinant that is phylogenetically conserved. The mechanisms for the expression of this determinant may differ among the normal and autoimmune strains.
Mayus
J L
JL
Pisetsky
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DS
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004247:DNA / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D007074:Immunoglobulin G / Q000096:biosynthesis; D007130:Immunoglobulin Idiotypes / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008817:Mice, Mutant Strains; D009194:Myeloma Proteins / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013045:Species Specificity
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000939:Epitopes; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D009194:Myeloma Proteins; D004247:DNA