Bk Virus Terminates Tolerance to Dsdna and Histone Antigens in Vivo

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Abstract
In order to characterize the immune response to BK virus, a human polyomavirus containing dsDNA and host cell histones, we followed the appearance of antibodies in five outbred rabbits after intravenous inoculation with purified infectious BK virus without any adjuvant. The animals were followed for 15 weeks after the first inoculation and booster doses were given after four and eight weeks. Antibodies were studied by ELISA techniques with the BK virus particle, dsDNA, ssDNA or the individual histones as test antigens. Antibodies to BK virus structural proteins were detected in all rabbits. Two out of five rabbits produced antibodies to dsDNA, ssDNA, nucleosomes and histones H1 and H3. Even a weak reactivity to H2B was detected in one serum. The autoantibody response was transient as it declined after a few weeks, but it reappeared after a second boost in one of the rabbits. The other animals did not respond in the same manner. The specificity of the antibodies against dsDNA was ascertained by inhibition studies employing S1 nuclease treated DNA as inhibitor. Furthermore, the dsDNA used as coating antigen was not recognized by a human reference serum with known specificity for ssDNA. The rabbit antisera did not show any reactivity to a panel of other (in this context irrelevant) autoantigens. This suggests that the anti-DNA and-histoneantibodies are not a result of non-specific polyclonal B cell activation. Thus, inoculation of dsDNA viruses may represent a new model that allows us to investigate mechanisms responsible for circumvention of tolerance to self molecules.