ANTIBODY RESPONSE IN HUMANS TO PIG XENOANTIGENS

人体器官捐赠者的短缺是世界上最大的限制 广泛使用移植作为治疗严重疾病的方法。 使用非人类物种，特别是猪，作为器官捐赠者 为解决捐赠器官短缺的问题提供了一个潜在的解决方案。它的用途 其他物种(异种移植)的组织移植在很大程度上是不成功的 因为对宿主免疫的本质缺乏了解 异种移植的反应和当前免疫抑制的失败 允许移植物长期存活的技术。的早期阶段 异种移植排斥反应以体液免疫为主 设计了在本申请中提出的响应和实验 要建立对主机的这一组件的更完整的了解 回应。我们打算找出控制病毒的免疫球蛋白基因。 猪组织接触患者的抗体反应(S)，分离物 并描述了具有功能能力的人类抗体 介导猪异种移植排斥反应，并鉴定特定亚群 产生这些抗体的B淋巴细胞。我们以前的 在啮齿动物身上的实验工作已经证明了异种移植的反应 似乎是一种独特的T细胞非依赖性抗体产生方式 由一组密切相关的免疫球蛋白基因控制。我们已经提议 这种类型的免疫反应是早期的共同特征 异种移植反应，即使对于不同的物种组合，以及 本提案中概述的实验旨在扩展这些 人对猪抗体反应检测的研究 异种移植物。我们相信，如果一小群与之密切相关的 免疫球蛋白基因负责控制体液 异种移植物在患者体内的反应，这一信息可能为 制定预防这种情况的新战略的基础 反应。

The shortage of human organ donors is a critical limitation in the widespread use of transplantation as a treatment for serious diseases. The use of non-human species, particularly the pig, as organ donors offers a potential solution to this shortage of donor organs. The use of tissues from other species (xenografts) has largely been unsuccessful because of a lack of understanding of the nature of the host's immune response to xenografts and the failure of current immunosuppressive techniques to allow for long-term graft survival. The early phases of the xenograft rejection reaction are dominated by humoral immune responses and the experiments proposed in this application are designed to establish a more complete understanding of this component of the host response. We intend identify the immunoglobulin genes that control the antibody response(s) mounted by patients exposed to pig tissues, isolate and characterize human antibodies that have the functional capacity to mediate rejection of pig xenografts, and identify the specific subsets of B lymphocytes that produce these antibodies. Our previous experimental work in rodents has demonstrated the xenograft response appears to be a unique form of T cell-independent antibody production controlled by a closely-related group of Ig genes. We have proposed that this type of immune response is a common feature of the early xenograft reaction, even for diverse species combinations, and the experiments outlined in this proposal are intended to extend these studies to an examination of the human antibody response to pig xenografts. We believe if a small group of closely-related immunoglobulin genes are responsible for controlling the humoral response of xenografts in patients, this information may provide the basis for the development of new strategies for preventing this reaction.