B cell reaponses and cardiac transplantation in infancy

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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.