EFFECTS OF MAJOR HISTOCOMPATIBILITY COMPLEX ON AUTOIMMUNE-DISEASE OF H-2-CONGENIC NEW-ZEALAND MICE

Autoimmune-prone NZB mice mainly produce IgM-class anti-DNA antibodies and mild SLE develops later in life. The F1 hybrid of NZB and non-autoimmune NZW mice (NZB/W F1 mice) develop a more fulminant SLE, associated with decreases In IgM class, and, In turn, increases in IgG class antl-DNA antibodies. To elucidate the role of the H-2 complex In this mode of anti-DNA antibody production, we established and studied H-2-congenic New Zealand mice, i.e. NZB, NZW, and NZB/W F1 mice with either the homozygous H-2x/H-2x or H-2d/H-2d haplotype or the heterozygous H-2d/H-2x haplotype. The data showed that: (I) although the nonH-2-linked NZB gene(s) seems to determine the IgM antl-DNA antibody production In NZB mice, the effect of this gene is fully expressed only in the case of the H-2d/H-2d homozygous state, (ii) The production of IgG antl-DNA antibodies observed in NZB/W F1 hybrid mice Is restricted to the H-2d/H-2x heterozygosity. (III) Because both NZB and NZW mice with the H-2d/H-2x haplotype produce a lower titer of IgG anti-DNA antibodies than do the NZB/W F1, mice, other complementary non-H-2-linked genetic elements from both NZB and NZW parents are required. The development of lupus nephritis correlated well with that of anti-DNA antibodies. Thus, H-2d/H-2xheterozygosity is a necessary but not sufficient condition for the development of autoimmunity in NZB/W F1 mice. We discuss the possibilities that these effects of the H-2 complex are linked to class II molecules and are fully expressed in association with other non-H-2-linked genetic elements. © 1990 Oxford University Press.