Characterization of B cell responses in relation to organ transplantation

Abstract

Antibody-mediated rejection is increasingly recognised within the transplantation community as a cause or contributing factor in the rejection of transplanted organs. The humoral immune response towards allografts involves B cells that, after T cell dependent activation, can differentiate into antibody producing cells. Whereas there are several therapeutic entities to treat cellular rejection, at present, no standard treatment for humoral rejection exists. The first part of this thesis describes the effects of different maintenance immunosuppressive drugs directly on B cells, as well as the effect on T cell help in vitro. The data presented in these chapters show differential effects of the drugs on B cells and T cell help. Furthermore, the effects of novel, experimental drugs on the in vitro activation of B cells are described. The second part of this thesis describes the development of a novel technique for monitoring the humoral alloimmune response. By using this technique, patients at risk for humoral rejection may be identified. The last part describes the difficulties and pitfalls of monitoring T cells that respond to alloantigen via the indirect pathway of allorecognition. In an alloimmune response, these are the T cells that provide help to B cells to become fully activated.