Involvement in lupus disease of idiotypes Id.F-423 and Id.IV-228 defined, respectively, upon foetal and adult MRL/Mp-lpr/lpr DNA-binding monoclonal autoantibodies.

The derivation of a monoclonal IgG3K autoantibody, designated F-423, from a foetal MRL/Mp-lpr/lpr mouse is described. It has immunochemical properties similar to DNA-binding monoclonal antibodies derived from adult mice with lupus disease in that it reacts with single-stranded DNA and, to a lesser extent, with double-stranded DNA and some forms of RNA. Its similarities to antibodies from adults extend further: it carries a public idiotype, Id.F-423, that can also be detected on antibodies from adult MRL and (NZB x NZW)F1 mice, and F-423 itself expresses other idiotypes defined originally on antibodies from adult lupus mice of both strains. Its potential involvement in pathological processes is demonstrated by two observations: (i) immunization of young MRL/Mp-+/+ mice with antibody F-423 induced the nephritic and immunological changes associated with systemic lupus erythematosus; and (ii) heterologous rabbit anti-Id.F-423 anti-idiotypic antibodies suppressed the progression of lupus disease in adult MRL/Mp-lpr/lpr mice. Similar effects were found with monoclonal antibody IV-228, an antibody derived from an adult MRL mouse and previously known to be directly nephrotoxic, and with anti-Id.IV-228 antibodies. It is concluded that even during foetal life mice of lupus-prone strains have lymphocytes capable of making pathogenic autoantibodies long before symptoms of lupus disease appear.