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 anti-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-2z/H-2z or H-2d/H-2d haplotype or the heterozygous H-2d/H-2z haplotype. The data showed that: (i) although the non-H-2-linked NZB gene(s) seems to determine the IgM anti-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 anti-DNA antibodies observed in NZB/W F1 hybrid mice is restricted to the H-2d/H-2z heterozygosity. (iii) Because both NZB and NZW mice with the H-2d/H-2z 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-2z heterozygosity is a necessary but not sufficient condition for the development of autoimmunity in NZB/W F1 mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirose
S
S
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Kinoshita
K
K
Nozawa
S
S
Nishimura
H
H
Shirai
T
T
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000235:genetics / Q000276:immunology
D001323:Autoantibodies; D006183:H-2 Antigens; D004247:DNA