Naturally occurring antibody response to DNA is associated with the response to retroviral gp70 in autoimmune New Zealand mice

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Abstract
The spontaneous occurrence of retroviral gp70 immune complexes (ICs) in the blood of autoimmune New Zealand Black and New (Zealand black × New Zealand white)F1 ([NZB × NZW]F1) mice is determined by a single dominant locus of the NZB strain (provisionally designated Agp-1). A combined effect of 2 unlinked dominant NZB loci (Ads-1 and Ads-2) is required for the production of anti-double-stranded DNA (anti-dsDNA) antibodies in these mice. The present genetic studies using (NZB × NZW)F1 × NZW backcross mice and their second through fourth generation progeny revealed that Agp-1 and Ads-1 exist in common or are closely linked on chromosome 17 of NZB mice and are related to the occurrence of renal disease. The renal disease and the serum level of both anti-dsDNA antibodies and gp70 ICs were more intense in (NZB × NZW)F1 hybrids than in NZB mice, indicating the contribution of NZW genes. In (NZB × NZW)F1 mice, a single dominant locus from the NZW strain, Agp-3, intensified the magnitude of gp70 IC formation, and a combined effect of 2 unlinked dominant loci from the NZW strain, Ads-3 and Ads-4, acted to increase the serum titers of antidsDNA antibodies. This study clearly indicates that the NZW loci Agp-3 and Ads-3 exist in common or are tightly linked on chromosome 17, are closely linked to the H-2 complex, and are associated with the severity of renal disease in (NZB × NZW)F1 hybrids. Thus, it is likely that the abnormalities involved in the antibody response to gp70 are in part genetically related to the production of autoantibodies to dsDNA as well as to the occurrence of renal disease in NZB and (NZB × NZW)F1 mice.