PAPER Induction of anti-DNA antibodies by immunization with anti-DNA antibodies: mechanism and characterization

Two well-characterized IgG monoclonal antibodies, reactive with double-stranded (ds) DNA and nucleosomes, were administered to normal BALB=c mice to examine the reproducibility and the biology of a previously reported model of anti-DNA antibody induction by immunization with anti-DNA antibodies. The monoclonal antibodies were purified either with or without a high-salt wash to remove nucleosomal antigens bound to them during the cell culture. Both monoclonal antibodies, but not normal IgG, induced significant IgG anti-dsDNA antibody production from 1 week to 25 weeks after the last immunization. The antibodies produced in this manner possess different binding preferences to ds synthetic polynucleotides than the antibodies used for the immunization, and they did not react with nucleosomes. The monoclonal antibodies purified with the high-salt wash were more effective in anti-DNA antibody induction than those purified without the high-salt wash. Even when bound to these monoclonal antibodies, neither dsDNA, nucleosomes, or ds synthetic polynucleotides exert significant antigenicity. For example, anti-DNA antibodies produced by mice immunized with an immune complex formed by poly(dA-dT) and one of the monoclonal antibodies that has a high affinity to this polynucleotide did not show an increased affinity to poly(dA-dT). Together, these results suggest that anti-DNA antibody molecules or processed antibody peptides, and not DNA=nucleosomes carried by anti-DNA antibodies, play a role in this model of anti-DN