ON THE BIOLOGICAL ORIGIN OF ANTI-DOUBLE-STRANDED (DS)DNA ANTIBODIES -SYSTEMIC LUPUS ERYTHEMATOSUS-RELATED ANTI-DSDNA ANTIBODIES ARE INDUCED BY POLYOMAVIRUS BK IN LUPUS-PRONE (NZBXNZW) F1 HYBRIDS, BUT NOT IN NORMAL MICE

We have recently demonstrated that polyomavirus BK and isolated BK dou ble-stranded (ds)DNA have a strong potential for induction of anti-dsD NA antibodies. Here, data are presented that demonstrate that normal m ice (a term used in this report for mice not predisposed to a lupus-li ke syndrome) of four different strains responded to both BK virus and BK dsDNA by producing transient antibodies binding preferentially to t he viral dsDNA itself. These antibodies did not bind in the Crithidia luciliae assay, and did not seem to be of pathogenic significance, as neither signs of proteinuria nor immunochemical signs of glomeruloneph ritis developed in these mice. In contrast, 5-week-old (NZBxNZW)F-1 mi ce developed strong and persistent anti-dsDNA antibodies in response t o BK virus and BK dsDNA, with similar features to those of anti-dsDNA antibodies from individuals with systemic lupus erythematosus: they re acted strongly in the Crithidia luciliae assay and cross-reacted with viral as well as with mammalian dsDNA. Furthermore, persistent protein uria and glomerulonephritis, with demonstrable heavy mesangial deposit s of immune complexes containing IgG anti-dsDNA antibodies, developed 2-3 months earlier than in spontaneously autoimmune control mice. The relevance of these observations to a viral origin of anti-dsDNA antibo dies in lupus is discussed.