Temporary breakdown of immunological tolerance to dsDNA and nucleohistone antigens in rabbits infected with rinderpest virus.

The rabbit-passaged L strain of rinderpest virus (RV) causes the transient induction of anti-nuclear antibodies (ANA) in rabbits. It has been shown by an indirect immunofluorescence test that the target antigens of these ANA are DNA and/or DNA-histone complexes (nucleohistone). Here detailed examinations of the target antigens were carried out by ELISA, and it was revealed that rabbit sera contained three types of antibodies: antibodies reacting equally with both dsDNA and ssDNA; those reacting with ssDNA alone; and those reacting with nucleohistone. Epitopes recognized by the third type consisted of complexes of dsDNA and H2A + H2B or of dsDNA and H2B. All types of antibodies were antigen specific. Since the diversity of ANA among experimental rabbits was large, it was suggested that genetic background is important in the induction of anti-dsDNA antibodies in this system. Moreover, early induction of antibodies to nucleohistone and the rapid disappearance of ANA suggest that B cell proliferation/maturation for continuous production of ANA requires factors other than RV infection. This system may help elucidate the mechanisms of ANA induction and the development of autoimmune diseases.