Characteristics of Auto Anti-idiotypic Antibodies Reactive with Antibodies Expressing the Pathogenic Idiotype, IdLNF1, in the (NZB×SWR)F1Model for Lupus Nephritis and its Parental Strains

Abstract

The F1cross 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, IdLNF1may play a role in the pathogenesis of this nephritis. The sera of SNF1mice, 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 IdLNF1Ig (IgG+IgM) deposition in the kidney glomerulus. Here, auto anti-IdLNF1antibody 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-IdLNF1antibody levels were decreased only in SNF1mice at 20–24 weeks of age. Auto anti-IdLNF1antibodies were purified by affinity chromatography; anti-IdLNF1antibodies derived from SNF1appeared to be of the Ab2β or γ type, while those from SWR mice were Ab2α. Thus, differences in the specificity of auto anti-idiotypic antibodies may be critical in the regulation of the IdLNF1idiotype in SWR and SNF1mice, and the development of nephritis in SNF1mice.