In mice with lupus nephritis qualitative changes in anti-DNA antibodies occur, such as IgG switch and increased cationic charge, to render these antibodies pathogenic. Pathogenic anti-DNA idiotypes can be encoded by genes of a normal mouse strain such as SWR, where they remain dormant. When the normal mice are crossed with an autoimmune strain like NZB, the F1 hybrids express these idiotypes owing to defects in immunoregulation, resulting in the development of lethal glomerulonephritis.