Idiotypic analysis of anti-nucleosome monoclonal antibodies derived from lupus mice

3F6 and 2E1 are anti-(H2A-H2B) monoclonal antibodies derived from a 12-month-old (NZBxNZW)F1 mouse that diverged from the same clonal precursor by somatic mutations. Rabbit anti-idiotypic antisera were prepared against these two monoclonal antibodies and used as probes to analyse the properties and expression of 3F6 and 2E1 idiotypes. Both idiotypes were conformational, distant from the antigen binding site and did not correlate with a VH- or VL-chain usage. 3F6 was preferentially bound by anti-3F6 idiotype but was weakly recognized by anti-2E1 idiotype suggesting, since 3F6 derives from 2E1, that 3F6 bore idiotypic determinants generated by somatic mutations. While none of the murine anti-DNA monoclonal antibodies tested expressed 2E1 or 3F6 idiotypes, 3F6 idiotype could be detected on approximately one-third of anti-(H2A-H2B) monoclonal antibodies derived from other lupus strains of mice, demonstrating the presence of cross-reactive idiotypes on autoantibodies directed against a nucleosome that could result from somatic mutations. (C) 1997 Academic Press Limited.