Hultman P, Bell L J, Eneström S, Pollard K M
Department of Pathology I, Linköping University, Sweden.
Clin Immunol Immunopathol. 1992 Nov;65(2):98-109. doi: 10.1016/0090-1229(92)90212-7.
Inbred, congenic, and intra-H-2-recombinant mouse strains were given subcutaneous injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl thrice weekly for 5-6 weeks. Mercury-treated mice from strains carrying the H-2s haplotype developed antinucleolar antibodies (ANoA), which targeted the 34-kDa nucleolar protein fibrillarin, and in some instances also nucleolar proteins of 60-70 and 10-15 kDa, the latter corresponding to histones. Strains with H-2b and H-2d haplotypes were resistant to induction of ANoA. The susceptibility to development of AnoA/antifibrillarin antibodies (AFA) was mapped to the H-2A-region using intra-H-2-recombinant strains. We were not able to confirm earlier reports that expression of H-2E genes dampens the development of ANoA. Mercury treatment caused a substantial increase in the titer of antichromatin (ACA) and/or antihistone (AHA) antibodies in a fraction of SJL/J, A.SW, A.TH, B10.S, and B10.HTT mice (H-2s), and in A/J (H-2k) mice, whereas mice from the C57BL/6J and C57BL/10J (H-2b), and the DBA and BALB/c (H-2d) strains were low or nonresponders. The development of AHA and ACA could not be linked to the H-2 complex. A significant, substantial increase of granular mesangial and systemic vessel wall IgG deposits occurred in mice with serum ANoA/AFA. However, the B10.S(9R) and B10.HTT strains, which express the H-2E genes, developed only an intermediately increased titer of mesangial IgG deposits. Systemic vessel wall IgG deposits occurred in only 60-80% of the B10.S(9R) mice and in none of the B10.HTT mice. This contrasted with the high titer of mesangial IgG deposits and uniform development of systemic vessel wall IgG deposits observed in B10.S mice not expressing H-2E. Mice with mesangial IgG deposits showed a mild glomerulonephritis. There was no systemic vasculitis. The susceptibility to development of ANoA, AHA, ACA, and systemic, granular IgG deposits in the B10.S strain was influenced by the sex, since males showed less uniform development of these immunopathologic features than females.
近交系、同源近交系和H-2基因座内重组小鼠品系每周皮下注射3次，每次注射1.6mg HgCl₂/kg体重或0.1ml NaCl，持续5 - 6周。携带H-2s单倍型的品系经汞处理的小鼠产生了抗核仁抗体（ANoA），该抗体靶向34kDa的核仁蛋白纤维原蛋白，在某些情况下还靶向60 - 70kDa和10 - 15kDa的核仁蛋白，后者对应于组蛋白。具有H-2b和H-2d单倍型的品系对ANoA的诱导具有抗性。利用H-2基因座内重组品系将对ANoA/抗纤维原蛋白抗体（AFA）产生的易感性定位到H-2A区域。我们无法证实早期关于H-2E基因表达会抑制ANoA产生的报道。汞处理导致一部分SJL/J、A.SW、A.TH、B10.S和B10.HTT小鼠（H-2s）以及A/J小鼠（H-2k）的抗染色质（ACA）和/或抗组蛋白（AHA）抗体滴度大幅升高，而C57BL/6J和C57BL/10J小鼠（H-2b）以及DBA和BALB/c小鼠（H-2d）品系的小鼠抗体滴度较低或无反应。AHA和ACA的产生与H-2复合体无关。血清中有ANoA/AFA的小鼠肾小球系膜和全身血管壁IgG沉积物显著大量增加。然而，表达H-2E基因的B10.S(9R)和B10.HTT品系仅出现系膜IgG沉积物滴度中度升高。全身血管壁IgG沉积物仅在60 - 80%的B10.S(9R)小鼠中出现，而在所有B10.HTT小鼠中均未出现。这与未表达H-2E的B10.S小鼠中观察到的高滴度系膜IgG沉积物和全身血管壁IgG沉积物均匀出现形成对比。有系膜IgG沉积物的小鼠表现出轻度肾小球肾炎。未出现全身性血管炎。B10.S品系对ANoA、AHA、ACA以及全身颗粒状IgG沉积物产生的易感性受性别影响，因为雄性小鼠这些免疫病理特征的发展不如雌性小鼠均匀。
