Geller R L, Bach F H, Turman M A, Casali P, Platt J L
Immunobiology Research Center, University of Minnesota, Minneapolis 55455.
Transplantation. 1993 Jan;55(1):168-72. doi: 10.1097/00007890-199301000-00031.
The rejection of organs transplanted between phylogenetically disparate species is thought to be initiated by the binding of naturally occurring antibodies of the recipient to the endothelium lining the blood vessels of the donor organ. We recently showed that among the xenoreactive natural antibodies in human serum that react with porcine endothelial cells and endothelial cell--derived glycoproteins are polyreactive antibodies. To test whether polyreactive natural antibodies are present in rejected xenografts we developed a series of hybridoma-derived antibodies specific for the polyreactive human monoclonal antibody 103, which we have shown to bind efficiently to porcine endothelial cells. Using these antiidiotypic reagents we detected antibodies bearing the 103 idiotype in a panel of human sera and on the surface of lymphocytes in the spleen of humans, rhesus monkeys, and baboons. The antiidiotypic reagents reacted in a pattern similar to the distribution of IgM, with immunoglobulin deposits in tissues obtained from pig-to-rhesus monkey and pig-to-baboon xenografts. Analysis of immunoglobulin eluted from these sites showed that they antibodies display the antigen-binding features of natural antibodies. Our findings are consistent with the hypothesis that idiotypes of polyreactive natural antibodies are broadly crossreactive. They also suggest that the polyreactive and xenoreactive IgM, which have been detected based on in vitro assays, may be deposited in a xenogeneic organ graft.
在系统发育上不同物种之间移植的器官发生排斥反应，被认为是由受体天然存在的抗体与供体器官血管内衬的内皮细胞结合所引发的。我们最近发现，在与猪内皮细胞和内皮细胞衍生糖蛋白发生反应的人血清异种反应性天然抗体中，存在多反应性抗体。为了测试多反应性天然抗体是否存在于被排斥的异种移植物中，我们开发了一系列针对多反应性人单克隆抗体103的杂交瘤衍生抗体，我们已证明该抗体能有效结合猪内皮细胞。使用这些抗独特型试剂，我们在一组人血清以及人、恒河猴和狒狒脾脏淋巴细胞表面检测到了带有103独特型的抗体。抗独特型试剂的反应模式与IgM的分布相似，在从猪到恒河猴和猪到狒狒的异种移植物获得的组织中有免疫球蛋白沉积。对从这些部位洗脱的免疫球蛋白的分析表明，它们具有天然抗体的抗原结合特征。我们的发现与多反应性天然抗体独特型具有广泛交叉反应性的假设一致。它们还表明，基于体外试验检测到的多反应性和异种反应性IgM可能沉积在异种器官移植物中。
