The pathogenesis of autoimmunity in New Zealand mice. IV. Independent stimulation of antibodies to DNA and RNA.

New Zealand mice spontaneously develop antibodies to double-stranded RNA and DNA. The appearance of these antibodies is accelerated by the administration of the synthetic double-stranded RNA, polyinosinic [unk] polycytidylic acid (poly I [unk] poly C). Since poly I [unk] poly C is known to act both as a nucleic acid antigen and as an adjuvant, the mechanism of nucleic acid antibody stimulation was studied to determine which property of poly I [unk] poly C was operative. NZB/NZW mice were made tolerant to poly I [unk] poly C as an antigen with cyclophosphamide. They were then given 10 μg or 150 μg of poly I [unk] poly C three times per week. Tolerant mice given 10 μg of poly I [unk] poly C had acceleration of antibodies to DNA but not RNA. In this case the stimulation of antibodies to DNA appeared to represent the adjuvant property of poly I [unk] poly C. Since non-tolerant but not tolerant mice had stimulation of antibodies to RNA with 10 μg poly I [unk] poly C, this anti-RNA acceleration appears to represent antigenic stimulation. All animals given 150 μg poly I [unk] poly C had stimulation of antibodies to both RNA and DNA, suggesting a predominently adjuvant mechanism. The possible role of antigenic and adjuvant properties of nucleic acids in the natural disease of New Zealand mice is discussed.