Noncognate function of B cells in transplantation

Abstract

How B cells affect the outcome of transplants is a question of enduring interest. Initial efforts to answer that question suggested, wrongly, that B cells have no impact on transplantation. Now, however, B cells are known to influence not only the outcome of vascularized grafts through the production of anti-donor antibodies but also the competence of cellular immunity through a number of physiologic functions. In this study, we explain why the importance of B cells was overlooked in the past and consider the range of noncognate functions of B cells that may determine the outcome of transplants.

Figure 1

Original experiments distinguishing the impact of cellular and antibody mediated responses. From [2]. The allantoic cavities of 12-day chick embryos were treated with 2.5 mg of testosterone propionate and then allowed to hatch. This treatment results in complete removal of the bursa and sometimes complete atrophy of the thymus. Shown in the table are the results from three different experiments done on bursaless chickens or bursaless chickens with an atrophic thymus. 1.) The ability of the blood of to produce lesions on the chorioallantoic membrane was tested, 2.) the ability of the chickens to reject skin grafts was tested, and 3.) the tuberculin reaction as a measure of delayed type hypersensitivity was tested.

Figure 2. Impact of antibodies on the outcome of organ versus cell or tissue transplants

A. Outcomes of organ transplants In solid organ transplantation donor and recipient vessels are anastomosed together thus hyperacute rejection is the first possible outcome. If hyperacute rejection is avoided antibodies may either cause acute vascular rejection, or accommodation. If acute vascular rejection is prevented and accommodation is not achieved, the graft may undergo cellular or chronic rejection. With the exception of cellular rejection, B cells are central to the other types of rejection because of the antibodies they produce. B. Outcome of cell and tissue transplants Unlike solid organ transplantation the blood vessels feeding a tissue or cell transplant are of recipient origin. As a result, humoral rejection is not observed. Early failure of a tissue or cell transplant is caused by primary non-function either due to failure of engraftment or a very rapid immune response. If engraftment occurs successfully the tissue or cells are then subject to cellular rejection only.