Idiotype restriction in murine lupus; high frequency of three public idiotypes on serum IgG in nephritic NZB/NZW F1 mice.
Antibodies to self-antigens are characteristic of several human and murine autoimmune diseases. Subsets of those autoantibodies cause organ damage in some instances, such as IgG antibodies to DNA in human and murine systemic lupus erythematosus (SLE). Our experiments in the NZB/NZW F1 (BW) female mouse model of SLE were designed to define idiotypic (Id) structures on antibodies to DNA in attempts to distinguish pathogens from nonpathogens within the anti-DNA population. Two important findings emerged. First, the number of public Id expressed became relatively restricted as the mice aged, with three such Id (IdX, IdGN1 and IdGN2) dominating and accounting for 30 to 95% of the total serum IgG in all individual nephritic mice studied, and 81 to 86% of the total IgG in serum pools from 30-wk-old nephritic mice. Second, IdGN1 and IdGN2 constituted approximately 50% of the IgG deposited in glomeruli of nephritic mice; IdX was present in negligible quantities in glomeruli, whereas it was usually the most frequent Id in BW serum. These latter findings suggested that pathogens and nonpathogens can be distinguished by their idiotypy in this animal model. The finding of relative Id restriction suggests the occurrence of an idiotypic "spreading" phenomenon, in which a regulatory process appears as BW mice age that results in repeated selection and expansion of this small number of Id, one group of which, the IdGN, is pathogenic. This process was further suggested in experiments in which IdX was suppressed by administration of anti-IdX; the "escape" antibodies to DNA appearing after suppression of IdX were composed largely of IdGN1 and IdGN2, without a major contribution from Id-negative mutants. Defining the basis of this Id spreading or restriction phenomenon may provide important information regarding the pathogenesis of this autoimmune disease.
D000367:Age Factors; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D004247:DNA / Q000276:immunology; D005921:Glomerulonephritis / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007678:Kidney Glomerulus / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB / Q000276:immunology
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D004247:DNA