Interactions between B-lymphocytes and Type 1 NKT cells in autoimmune diabetes

Abstract

Type 1 diabetes is one of the most prevalent autoimmune conditions that develops during childhood and has an increasing incidence worldwide. The disease results from the destruction of pancreatic β cells mediated by autoreactive T-lymphocytes. In order to develop preventive therapies, the cellular mechanisms responsible for the generation and activation of β cell-specific T-lymphocytes need to be characterized. Recent studies in the NOD mouse model of autoimmune diabetes suggest that the MHC Class II presentation of β cell-derived antigens by B-lymphocytes could support the development and activity of autoreactive CD4+ T-lymphocytes in this disease. Interestingly, B-lymphocytes are also the most frequent antigen presenting cells expressing the MHC Class I like molecule, CD1d, the restriction molecule responsible for presentation of lipid and glycolipid antigens to Type 1 NKT cells. Splenic marginal zone B-lymphocytes, which express CD1d at particularly high levels, seem poised to signal to Type 1 NKT cells. In contrast to the disease-promoting role of conventional CD4+ T-lymphocytes, several lines of evidence have shown that Type 1 NKT cells are involved in the prevention of Type 1 Diabetes. This review will analyze current knowledge on the roles of B-lymphocytes and Type 1 NKT cells in the onset of Type 1 Diabetes and explore possible outcomes of their interactions in relation to disease.