The NZB X SWR model of lupus nephritis. II. Autoantibodies deposited in renal lesions show a distinctive and restricted idiotypic diversity

Abstract

The F1 progeny (SNF1) derived from crossing autoimmune NZB with normal SWR mice uniformly develop lethal glomerulonephritis in marked contrast to the NZB parents. In the preceding paper we found qualitative and idiotypic differences between the anti-DNA antibodies produced by the SNF1 mice and their NZB parents. We identified two clusters of interrelated cross-reactive idiotypic (CRI) families among the SNF1-derived autoantibodies. Here we analyzed the idiotypic profile of the broad spectrum of immunoglobulins deposited in the nephritic kidneys of SNF1 mice and found a restricted idiotypic diversity. To establish that the autoantibody idiotypes detected in the renal lesions were not there as a result of nonspecific trapping, five separate batches of kidney eluates obtained from 100 SNF1 kidneys were analyzed. Both during early and late stages of nephritis, the predominant and consistent idiotypic markers of antibodies in the renal lesion of SNF1 mice were those shared by the two clusters of anti-DNA CRI families. We have termed these nephritogenic idiotypic markers collectively as idiotypes-lupus nephritis-SNF1 or IdLNF1. The Id564 family that encompasses a set of SNF1-derived highly cationic anti-DNA antibodies bearing the normal SWR parent's allotype was more prominently represented in the SNF1 kidneys with early nephritis. Although cationic antibodies were prevalent, the IdLNF1 markers were present on both cationic and anionic or neutral antibodies in the renal lesions of SNF1 mice, and the Ig allotypes of both parents were equally represented in those nephritogenic antibodies. The IdLNF1 positive family of antibodies were also found in high levels in the sera of old SNF1 mice, but they could not be detected in the sera of NZB or SWR mice, nor were they present in the immunoglobulins deposited in the kidneys of rare old NZB mice. The results suggest that select families of nephritogenic idiotypes that are dormant in the autoimmune NZB and the normal SWR parents become expressed in the SNF1 progeny due to genetic and immunoregulatory defects.