Characteristics of auto anti-idiotypic antibodies reactive with antibodies expressing the pathogenic idiotype, IdLNF1, in the (NZB x SWR)F1 model for lupus nephritis and its parental strains.
The F1 cross between SWR and NZB mice, SNF1, develops severe immune complex glomerulonephritis, in a similar manner to humans with systemic lupus erythematosus (SLE). Our previous data indicate that the idiotypically-related family of antibodies, IdLNF1 may play a role in the pathogenesis of this nephritis. The sera of SNF1 mice, but not NZB or SWR, contained high titers of IdLNF1+ IgG antibodies, which peaked at 22-24 weeks, coinciding with an increase in the CD4 to CD8 ratio of IdLNF1-reactive T cells and IdLNF1 Ig (IgG + IgM) deposition in the kidney glomerulus. Here, auto anti-IdLNF1 antibody levels were quantitated as the mice aged and were found to be significantly different in the three strains, particularly after 20 weeks of age. Moreover, auto anti-IdLNF1 antibody levels were decreased only in SNF1 mice at 20-24 weeks of age. Auto anti-IdLNF1 antibodies were purified by affinity chromatography; anti-IdLNF1 antibodies derived from SNF1 appeared to be of the Ab2 beta or gamma type, while those from SWR mice were Ab2 alpha. Thus, differences in the specificity of auto anti-idiotypic antibodies may be critical in the regulation of the IdLNF1 idiotype in SWR and SNF1 mice, and the development of nephritis in SNF1 mice.
Uner
A H
AH
Department of Microbiology, SUNY Health Science Center at Syracuse 13210, USA.
Tatum
A H
AH
Knupp
C J
CJ
Gavalchin
J
J
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001667:Binding, Competitive; D002678:Chimera / Q000276:immunology; D003433:Crosses, Genetic; D004277:DNA, Single-Stranded / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007075:Immunoglobulin M; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D008814:Mice, Inbred NZB; D018448:Models, Immunological
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M