Stuffers-Heiman M, Günther E, van Es L A
Immunology. 1979 Apr;36(4):759-67.
Induction of autoimmune antibodies against antigens of glomerular basement membrane (GBM) was studied in nine inbred strains of rats each with a different major histocompatibility complex H-1. Brown-Norway (BN) (H-1n), Lewis (H-1(1)), PVG/c (H-1c), AS2 (H-1f), AVN (H-1a), BD V (H-1d), DA (H-1a) and F344 (H-1(1)) rats were immunized with bovine GBM and Freund's complete adjuvent (CFA). A pronounced linear deposition of host IgG (IgG1 and IgG2a) along the GBM was found in BN rats. No deposition of C3 could be detected in the glomeruli nor did the animals develop proteinuria. The quantity of autoimmune antibodies fixed to the GBM was low (48 microgram +/- 14) which could explain the absence of C3 deposition and proteinuria. The antigenic specificity of the antibodies deposited along the GBM in BN rats was shown by the fixation in vitro of the eluted antibodies to the GBM and tubular basement membrane (TBM) of normal kidneys. A much weaker and irregular deposition of host IgG along the GBM was observed in PVG/c, AS2. AVN, BD V, DA and F344 rats. Of these strains, eluates from the glomeruli of PVG/c, AVN, BD V and DA rats fixed very weakly to the GBM of normal kidneys whereas eluates from AS2 and F344 rats did not fix to GBM or TBM. No deposition of host IgG was found in Lewis rats, and the eluates did not fix to normal kidneys. Congenic L.BN rats with the BN H-1n haplotype and a Lewis background did not respond. This study shows a genetic predisposition in rats to an autoimmune anti-GBM response which is not, or not exclusively, controlled by genes linked to the H-1 histo-compatibility complex.
在九个具有不同主要组织相容性复合体H-1的近交系大鼠中，研究了针对肾小球基底膜（GBM）抗原的自身免疫抗体的诱导情况。用牛GBM和弗氏完全佐剂（CFA）免疫了棕色挪威（BN）（H-1n）、刘易斯（H-1(1)）、PVG/c（H-1c）、AS2（H-1f）、AVN（H-1a）、BD V（H-1d）、DA（H-1a）和F344（H-1(1)）大鼠。在BN大鼠中发现宿主IgG（IgG1和IgG2a）沿GBM有明显的线性沉积。在肾小球中未检测到C3沉积，动物也未出现蛋白尿。固定在GBM上的自身免疫抗体量较低（48微克±14），这可以解释C3沉积和蛋白尿的缺失。通过将洗脱的抗体在体外固定到正常肾脏的GBM和肾小管基底膜（TBM）上，显示了BN大鼠中沿GBM沉积的抗体的抗原特异性。在PVG/c、AS2、AVN、BD V、DA和F344大鼠中，观察到宿主IgG沿GBM的沉积要弱得多且不规则。在这些品系中，PVG/c、AVN、BD V和DA大鼠肾小球的洗脱物与正常肾脏的GBM结合非常弱，而AS2和F344大鼠的洗脱物不与GBM或TBM结合。在刘易斯大鼠中未发现宿主IgG沉积，其洗脱物也不与正常肾脏结合。具有BN H-1n单倍型和刘易斯背景的同源L.BN大鼠没有反应。这项研究表明，大鼠对自身免疫性抗GBM反应存在遗传易感性，这种易感性并非或并非完全由与H-1组织相容性复合体相关的基因控制。
