Specificity and idiotypic analysis of a monoclonal anti-Sm antibody with anti-DNA activity.
To investigate the mechanisms of anti-Sm expression in murine systemic lupus erythematosus (SLE), the idiotypic determinants of a monoclonal anti-Sm antibody were studied. This antibody, 2G7, was derived from the fusion of spleen cells of an autoimmune MRL-lpr/lpr mouse with the 653 myeloma. Specificity for Sm was demonstrated by an ELISA with the use of affinity-purified Sm as well as immunoprecipitation of radiolabeled RNA. An anti-2G7 antiserum was prepared in a rabbit and rendered specific for idiotype by extensive absorption against BALB/c and MRL-lpr/lpr monoclonal proteins. The resulting antiserum detected determinants found on 2G7 as well as on two MRL anti-DNA antibodies, 6/P and 6/N, an independently derived MRL-lpr/lpr anti-Sm called 7.13, and the BALB/c myeloma FLOPC 21. Two distinct determinants could be demonstrated by the creation of cross-reactive idiotype systems by using the various monoclonal antibodies as ligands for the anti-idiotype. Both idiotypes were demonstrated in sera of normal and autoimmune mice, although MRL +/-/+/- mice had the highest levels of strains tested. To explain the pattern of idiotypic relatedness, 2G7 was tested for anti-DNA activity by ELISA. 2G7 displayed activity for single-stranded DNA as well as synthetic DNA and RNA homopolymers. Absorption analysis indicated that the anti-DNA and anti-Sm binding activities were the product of the same antibody. These results suggest that anti-Sm and anti-DNA may be related by both idiotype and antigenic specificity, providing a mechanism for their common expression in SLE.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis* / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000032:analysis* / Q000096:biosynthesis; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D006825:Hybridomas / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000032:analysis*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; 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; D011817:Rabbits; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000941:Antigens; D001324:Autoantigens; D007130:Immunoglobulin Idiotypes; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D004247:DNA