Interactions between B-lymphocytes and type 1 NKT cells in autoimmune diabetes.
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 beta cells mediated by autoreactive T-lymphocytes. In order to develop preventive therapies, the cellular mechanisms responsible for the generation and activation of beta 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 beta 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.
Comparative Genomics Centre, James Cook University, Townsville, Queensland, Australia.
François D
FD
Dufour
Pablo A
PA
Silveira
Alan G
AG
Baxter
D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology*; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D015398:Signal Transduction / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology
D018949:Antigens, CD1; D055610:Antigens, CD1d; C526877:CD1D protein, human