MONOCLONAL ANTI-DNA ANTIBODIES - STRUCTURE, SPECIFICITY, AND BIOLOGY

Anti-DNA antibodies are a major contributor to the pathogenesis associ ated with the autoimmune disease systemic lupus erythematosus in mice and human. The accumulation of a large body of structural information on autoimmune anti-DNA antibodies over the past several years, particu larly from mice, has provided considerable insight into the structure, function, and biology of this important class of autoantibodies. Even though the germline repertoire of light and heavy chain variable regi ons that may encode DNA-specific antibodies is very large in mice, the re are individual light and heavy chain variable region genes that hav e been recurrent and preferentially expressed among anti-DNA hybridoma s. This has been particularly true for hybridomas producing antibodies that bind duplex, B-form, mammalian DNA (dsDNA). Recurrent somaticall y derived variable region structures, particularly arginines in the th ird complementary-determining region of the heavy chain (VH-CDR3), hav e also been recurrent and preferentially expressed among monoclonal an ti-DNA antibodies. In fact specificity for dsDNA can be correlated to the relative amino acid position at which arginines are expressed with in VH-CDR3 of anti-DNA. Most important from the results of structural analyses of monoclonal anti-DNA autoantibodies has been the realizatio n that autoimmunity to DNA results from a clonally selective, antigen- specific immune response to DNA. Autoimmune antibodies to DNA have all of the characteristics of secondary immune antibodies. In further sup port of this hypothesis, we have been able to induce anti-DNA antibodi es in normal, nonautoimmune mice by immunization with immunogenic DNA- peptide complexes. The induced antibodies have all of the structural a nd functional characteristics of autoimmune anti-DNA including the pat hogenetic potential to induce glomerulonephritis. This review summariz es the results of research from our laboratory that support the above conclusions. (C) 1997 Academic Press, Inc.