ANTIGEN-SPECIFIC INDUCTION OF ANTIBODIES AGAINST NATIVE MAMMALIAN DNAIN NONAUTOIMMUNE MICE

Spontaneous anti-DNA antibodies in autoimmune mice have the characteri stics of antibody produced by Ag-specific, clonally selective B cell s timulation. The nature of the somatically derived antibody V region st ructures recurrent among spontaneous anti-DNA antibodies suggests that DNA or DNA-protein complexes may provide the antigenic stimulus for a utoimmune anti-DNA antibody. In order to test this hypothesis directly , we have immunized normal, nonautoimmune-predisposed mice with comple xes formed with DNA and an immunogenic, DNA-binding peptide. The highl y immunogenic peptide, Fus1, forms an internal domain of a 128-amino a cid ubiquitin-fusion protein from Trypanosoma cruzi. DNA-Fus1 complexe s formed with native calf thymus DNA induced anti-DNA antibody in norm al, nonautoimmune-predisposed mice that is similar in isotype and spec ificity to spontaneous anti-DNA antibody in (NZB x NZW)F1 autoimmune m ice. The progressive nature of the development of dsDNA specificity in the immunized mice was also analogous to what is observed in the spon taneous anti-DNA antibody response of autoimmune (NZB x NZW)F1 mice. D NA-Fus1 immunized mice that produced IgG that bound to dsDNA had low t o moderate levels of proteinuria and glomerular deposits of IgG. This experimental immunization system may be useful for understanding the i mmunologic basis for autoimmunity to DNA.