The diverse roles of human B lymphocytes in renal transplantation

Renal transplantation is the treatment of choice for patients with end stage renal disease. Despite the significant advances made over the last fifty years, one predicament that still perplexes the transplant community is late allograft loss. The two major contributing factors include the limitations with the clinical utility of various markers for early diagnosis and lack of appropriate therapy. This thesis deals with the issue of early diagnosis and tries to establish a link between the clinical, histological and immunological phenotype with a view to identify prognostic markers. Firstly, low-grade proteinuria is clinically analysed for its utility to predict graft outcomes. Secondly, a disjunction between the clinical and histological phenotype and more importantly the limited utility of the clinical phenotype to determine the prognosis for a troubled allograft in light of clinical dysfunction is considered. Thirdly, a novel definition of human B regulatory cells is proposed with a view to address the discrepancy in the current literature with regards to their identification. Fourthly, a link between the histological phenotype of late allograft dysfunction is correlated with the frequency and function of regulatory B cells. Here, the functional diversity of the B cells, specifically within a small sub-group of B regulatory cells in relation to histological abnormalities is considered. Finally, the phenotype and functionality of the Bregs are explored for their use as potential markers for allograft outcomes and the utility of a simple phenotype tested in a prospective sample of patients from a randomized controlled trial.