By assessing the development of Y-linked autoimmune acceleration (Yaa) 
gene-induced systemic lupus erythematosus in C57BL/6 (B6) x (New Zealand Black 
(NZB) x B6.Yaa)F(1) backcross male mice, we mapped three major susceptibility 
loci derived from the NZB strain. These three quantitative trait loci (QTL) on 
NZB chromosomes 1, 7, and 13 differentially regulated three different autoimmune 
traits: anti-nuclear autoantibody production, gp70-anti-gp70 immune complex 
(gp70 IC) formation, and glomerulonephritis. Contributions to the disease traits 
were further confirmed by generating and analyzing three different B6.Yaa 
congenic mice, each carrying one individual NZB QTL. The chromosome 1 locus that 
overlapped with the previously identified Nba2 (NZB autoimmunity 2) locus 
regulated all three traits. A newly identified chromosome 7 locus, designated 
Nba5, selectively promoted anti-gp70 autoantibody production, hence the 
formation of gp70 IC and glomerulonephritis. B6.Yaa mice bearing the NZB 
chromosome 13 locus displayed increased serum gp70 production, but not gp70 IC 
formation and glomerulonephritis. This locus, called Sgp3 (serum gp70 production 
3), selectively regulated the production of serum gp70, thereby contributing to 
the formation of nephritogenic gp70 IC and glomerulonephritis, in combination 
with Nba2 and Nba5 in NZB mice. Among these three loci, a major role of Nba2 was 
demonstrated, because B6.Yaa Nba2 congenic male mice developed the most severe 
disease. Finally, our analysis revealed the presence in B6 mice of an H2-linked 
QTL, which regulated autoantibody production. This locus had no apparent 
individual effect, but most likely modulated disease severity through 
interaction with NZB-derived susceptibility loci.