Abstract

Both in animal models and in human systemic lupus erythematosus (SLE) the occurrence of nephritogenic autoantibodies bearing dominant idiotypes has been described. In this study we investigate the relation between the induction pathway of polyclonal B cell activation and the production and glomerular deposition of nephritogenic antibodies with shared dominant idiotype(s). Polyclonal B cell activation was induced in several experimental models characterized by glomerular immune deposit formation. We monitored the occurrence of dominant idiotypes among immunoglobulins deposited in the glomeruli. In addition, we studied the species specificity of the dominant idiotypes, by monitoring their presence in kidney sections of patients with an immunologically mediated kidney disease. Anti-idiotype antisera against two monoclonal anti-DNA autoantibodies were used, derived from MRL-lpr/lpr mice, i. e. clone H241 and clone H130. Autoantibodies with the H241 idiotype were present in immune complex depositions in all experimental models but not in humans. We therefore conclude that the presence of this dominant idiotype is independent of the induction pathway of polyclonal B cell activation. However, autoantibodies bearing the H130 idiotype were only detected in kidney sections of mice with spontaneous lupus.

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