Kawano H, Abe M, Zhang D, Saikawa T, Fujimori M, Hirose S, Shirai T
Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Clin Immunol Immunopathol. 1992 Dec;65(3):308-14. doi: 10.1016/0090-1229(92)90162-h.
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.
在表型正常的新西兰白兔（NZW，H-2z）与易患系统性红斑狼疮（SLE）的Bxsb小鼠（H-2b）的F1杂交后代中，无论是否存在Yaa（Y染色体连锁自身免疫加速）突变基因，疾病特征都比Bxsb小鼠更为严重。为了确定与NZW小鼠主要组织相容性复合体（MHC）相关的基因是否参与了这一过程，我们培育了H-2同基因NZW.H-2d品系，并比较了（NZW×Bxsb）F1（H-2z/b）和（NZW.H-2d×Bxsb）F1小鼠（H-2d/b）自身免疫性疾病的严重程度。与Bxsb小鼠相比，两性的H-2z/b杂合F1小鼠（而非H-2d/b）出现蛋白尿的发病率更高且加速，血小板减少症更严重。在NZW×（NZW×Bxsb）F1回交小鼠中，H-2z/b杂合后代比H-2z/z纯合子表现出更严重的疾病。因此，（NZW×Bxsb）F1小鼠中的疾病加速事件与H-2z/b杂合性相关。由于H-2d/z杂合性在（NZB×NZW）F1小鼠的SLE中起关键作用，而（NZB×NZW）F1小鼠的SLE特征与（NZW×Bxsb）F1小鼠不同，目前的观察结果可能意味着不同但相关的MHC杂合性在这些不同的SLE综合征中作为一种易感遗传因素起作用。
