Heterozygosity of the major histocompatibility complex controls the autoimmune disease in (NZW x BXSB) F1 mice.
In the F1 hybrid of phenotypically normal NZW (H-2z) and systemic lupus erythematosus (SLE)-prone BXSB mice (H-2b), features of the disease became more severe than those seen in the BXSB mice, regardless of the presence or absence of the Yaa (Y-chromosome-linked autoimmune acceleration) mutant gene. To determine whether the gene(s) linked to the major histocompatibility complex (MHC) of NZW mice is involved in this event, we developed the H-2-congenic NZW.H-2d strain and compared the severity of autoimmune disease between (NZW x BXSB) F1 (H-2z/b) and (NZW.H-2d x BXSB) F1 mice (H-2d/b). The H-2z/b, but not H-2d/b, heterozygous F1 mice of both sexes showed an accelerated, higher incidence of proteinuria and a more severe thrombocytopenia than did the BXSB mice. In NZW x (NZW x BXSB) F1 backcross mice, the H-2z/b heterozygous progeny showed more severe disease than did the H-2z/z homozygotes. Thus, disease-accelerating events in (NZW x BXSB) F1 mice are linked to the H-2z/b heterozygosity. Because H-2d/z heterozygosity plays a crucial role for SLE in (NZB x NZW) F1 mice, in which SLE features differ from those in (NZW x BXSB) F1 mice, the present observations may imply that the different but related MHC heterozygosity acts as a predisposing genetic element in these different SLE syndromes.
Kawano
H
H
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Abe
M
M
Zhang
D
D
Saikawa
T
T
Fujimori
M
M
Hirose
S
S
Shirai
T
T
D000367:Age Factors; D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010976:Platelet Count
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D006183:H-2 Antigens