CHARACTERISTICS OF AUTO ANTIIDIOTYPIC ANTIBODIES REACTIVE WITH ANTIBODIES EXPRESSING THE PATHOGENIC IDIOTYPE, ID(LN)F(1), IN THE (NZBXSWR)F-1 MODEL FOR LUPUS NEPHRITIS AND ITS PARENTAL STRAINS

The F-1 cross between SWR and NZB mice, SNF1, develops severe immune c omplex glomerulonephritis, in a similar manner to humans with systemic lupus erythematosus (SLE). Our previous data indicate that the idioty pically related family of antibodies, Id(LN)F(1) may play a role in th e pathogenesis of this nephritis. The sera of SNF1 mice, but not NZB o r SWR, contained high titers of Id(LN)F(1)(+) IgG antibodies, which pe aked at 22-24 weeks, coinciding with an increase in the CD4 to CD8 rat io of Id(LN)F(1)-reactive T cells and Id(LN)F(1) Ig (IgG+IgM) depositi on in the kidney glomerulus. Here, auto anti-Id(LN)F(1) antibody level s were quantitated as the mice aged and were found to be significantly different in the three strains, particularly after 20 weeks of age. M oreover, auto anti-Id(LN)F(1) antibody levels were decreased only in S NF1 mice at 20-24 weeks of age. Auto anti-IdL(LN)F(1) antibodies were purified by affinity chromatography; anti-Id(LN)F(1) antibodies derive d 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 th e Id(LN)F(1) idiotype in SWR and SNF1 mice, and the development of nep hritis in SNF1 mice. (C) 1998 Academic Press.