B cell reaponses and cardiac transplantation in infancy

该项目的总体目标是确定婴儿期接受胸腺切除术、短暂性T细胞消耗和免疫抑制治疗的心脏移植受者是否会在B细胞室中发生缺陷。在这些儿童中，T细胞区对缺乏新T细胞产生和短暂T细胞耗竭的补偿可能导致T细胞库严重收缩和T细胞功能改变。由于蛋白质抗原抗体和B细胞记忆反应的产生需要T细胞的帮助，这些变化可能会改变B细胞区室参与宿主防御和调节自身免疫的能力。本项目提出的研究将探讨胸腺切除术（在心脏手术的非移植受试者中）和T细胞消耗和免疫抑制（在婴儿期心脏移植受者中）所带来的T细胞室功能特性的改变是否会损害T细胞依赖性和T细胞非依赖性抗体反应、B细胞记忆的产生和/或维持、B细胞受体多样性和自身抗体的产生。这些研究将首次系统地分析心脏移植受者的B细胞反应

The overall goal of this project is to determine whether recipients of cardiac transplants in infancy treated with thymectomy, transient T cell depletion and immunosuppression develop defects in the B cell compartment. In these children, compensation of the T cell compartment for the lack of new T cell production and transient T cell depletion may cause a severely contracted T cell repertoire and altered T cell function. Since production of antibodies to protein antigens and B cell memory responses require T cell help, these changes could modify the ability of the B cell compartment to attend to host defense and to regulate auto-immunity. The research proposed in this project will explore whether altered functional properties of the T cell compartment brought about by thymectomy (in non transplanted subjects of cardiac surgery) and T cell depletion and immunosuppression (in recipients of cardiac transplants in infancy) impair T cell-dependent and T cell independent antibody responses, the generation and/or maintenance of B cell memory, B cell receptor diversity and autoantibody production. These studies will be the first to systematically analyze B cell responses in recipients of cardiac transplants in infancy and will produce new fundamental knowledge and insights into how host defense can be improved, in part through the design of more efficient immunization. The project will study patients with cardiac transplants and non-transplant cardiac surgery early in life through collaboration with Project 1. To investigate the mechanisms by which thymectomy, T cell depletion, immunossupression and cardiac allotransplantation may depress B cell responses and to test strategies to improve B cell memory responses, the project will study mice (C57BL/6). The evaluation of the B cell responses will involve collaborations with Project 3 for determining T cell "help" competency, and with Project 4 to analyze B cell responses in cynomolgus monkeys.