A new role for an old player: do B cells unleash the self-reactive CD8+ T cell storm necessary for the development of type 1 diabetes?

Type I diabetes mellitus is an autoimmune disease mediated by a selective immune-mediated destruction of the insulin containing beta cells within the pancreatic islets of Langerhans. T cells reactive to beta cell-derived antigens are critical for the pathogenesis of type I diabetes, indeed treatments that target T cells are currently in clinical trials. CD8+ T cells may play a particularly crucial role in the onset of hyperglycaemia, as they can mediate beta cell destruction late in the pathogenesis of diabetes. However, the precise steps by which beta cell-reactive CD8+ T cells are activated are poorly understood. In this review we speculate on the possibility that B cells are essential for the activation and expansion of pathogenic CD8+ T cells that cause final beta cell destruction. We also discuss the involvement of different B cell subsets in the aetiology of diabetes.