Ohdan Hideki, Sykes Megan
Department of Surgery, Division of Frontier Medical Science, Programmes for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Xenotransplantation. 2003 Mar;10(2):98-106. doi: 10.1034/j.1399-3089.2003.02108.x.
Xenotransplantation of pig organs to humans is a possible solution to the shortage of donor organs for transplantation. Multiple immunologic barriers need to be overcome if pig-to-primate transplantation is to be successful. The presence, in humans, of natural antibodies (Abs) directed against Galalpha1-3Galbeta1-4GlcNAc epitopes on pig vascular endothelium provides the major barrier, as antibody-antigen binding initiates the process of hyperacute rejection. Even if hyperacute rejection is prevented, acute vascular rejection develops. Acute vascular rejection is also mediated, in part, by xenoreactive Abs and may be complement-independent. Efforts being made to overcome antibody-mediated rejection include depletion of antibody by extracorporeal immunoadsorption, prevention of an induced Ab response by pharmacologic reagents, B-cell and/or plasma cell depletion, depletion or inhibition of complement, and the use of organs from pigs transgenic for human complement regulatory proteins. The ultimate solution would be the induction of B-cell tolerance to xenogeneic antigens, which is being explored by attempting to induce xenogeneic hematopoietic chimerism. Here, we review the properties of the B cell types responding to xenoantigens and the strategies for tolerizing those B cells.
将猪器官异种移植到人类体内是解决移植供体器官短缺问题的一种可能方法。如果猪到灵长类动物的移植要取得成功，就需要克服多个免疫障碍。人类体内存在针对猪血管内皮细胞上Galα1-3Galβ1-4GlcNAc表位的天然抗体，这是主要障碍，因为抗体-抗原结合会引发超急性排斥反应。即使预防了超急性排斥反应，也会发生急性血管排斥反应。急性血管排斥反应部分也是由异种反应性抗体介导的，可能与补体无关。为克服抗体介导的排斥反应所做的努力包括通过体外免疫吸附清除抗体、用药物试剂预防诱导性抗体反应、清除B细胞和/或浆细胞、清除或抑制补体，以及使用转人补体调节蛋白基因的猪的器官。最终的解决方案是诱导B细胞对异种抗原产生耐受性，目前正在通过尝试诱导异种造血嵌合体来探索这一方法。在此，我们综述了对异种抗原作出反应的B细胞类型的特性以及使这些B细胞产生耐受性的策略。
