Distinct clonotypes of anti-DNA antibodies in mice with lupus nephritis

Clonotypes of IgG anti-DNA antibodies were studied by isoelectric focusing in various autoimmune mice with or without lethal lupus nephritis. MRL/MpJ-lpr/lpr mice exhibited the most heterogeneous spectrotypes of anti-DNA antibodies in the pH range from 6.5 to 8.5, with marked variation in individual mice. Female (NZB X NZW)F1 mice expressed rather uniform DNA-binding bands composed of at least five to six distinct subgroups, having isoelectric points from 6.5 to 8.0. Male BXSB mice showed major characteristic bands confined to alkaline pH range from 7.8 to 8.5, similar to C57BL/6J-lpr/lpr mice, which showed markedly restricted bands in this region. Both AKR/J-lpr/lpr and C3H/HeJ-lpr/lpr mice expressed DNA-binding bands mostly focused between pH 6.5 and 8.2. The aging study indicated that three autoimmune mice (MRL/MpJ-lpr/lpr, [NZB X NZW]F1, and male BXSB) that developed fatal glomerulonephritis showed clonal expansion of anti-DNA antibodies throughout their life. In contrast, such age-dependent expansion of anti-DNA clonotypes was not evident in three lpr cogenic mice (C57BL/6J-lpr/lpr, AKR/J-lpr/lpr, and C3H/HeJ-lpr/lpr) that developed only mild glomerulonephritis; rather, their expression of anti-DNA spectrotypes diminished as they aged. Anti-DNA activities in renal eluates from nephritic autoimmune mice were mostly distributed in the pH range from 6.5 to 8.0, without significant concentrations in the high alkaline range of more than pH 8.0. These results suggest that there exist distinct anti-DNA clonotypes in each mouse strain and that the development of lupus nephritis does not appear to be associated with particular spectrotypes of anti-DNA antibodies. Rather, the age-dependent expansion of anti-DNA clonotypes may be a feature more characteristic of mice developing lethal lupus nephritis.