To investigate the specific contribution of select MHC class II genes on the 
development of murine lupus, H-2 congenic (NZB x BXSB)F1 hybrid mice bearing 
either H-2b/b, H-2d/b, or H-2d/d haplotypes were generated. We compared the 
clinical development (autoantibody production and glomerulonephritis) of 
systemic lupus erythematosus (SLE) in these three F1 hybrids in the presence or 
absence of the mutant gene, Yaa (Y chromosome-linked autoimmune acceleration), 
which normally accelerates the progression of murine SLE. (NZB x BXSB)F1 hybrid 
female mice bearing either the H-2b/b or H-2d/b haplotype developed a rapid 
course of severe SLE, while the appearance of disease was markedly delayed in 
H-2d/d hybrid females. However, in the presence of the Yaa gene, H-2d/d F1 males 
developed SLE as severe as H-2b/b and H-2d/b F1 males. These data indicate that 
(a) the conventional H-2b is a haplotype leading to susceptibility for murine 
SLE, while H-2d is a relatively resistant haplotype; (b) the H-2b haplotype 
exhibits a dominant effect on autoimmune responses, similar to the classical 
MHC-linked Ir gene effect; and (c) most strikingly, the Yaa gene totally 
abrogates the MHC effect on murine lupus in (NZB x BXSB)F1 hybrid mice.