B-lymphocytes expressing an immunoglobulin specificity recognizing the pancreatic ß-cell autoantigen peripherin are potent contributors to type 1 diabetes development in NOD mice.
Diabetes 2016 Jul; 65:1977-87.
While the autoimmune destruction of pancreatic ß-cells underlying type 1 diabetes (1D) development is ultimately mediated by T-cells in NOD mice and also likely humans, B-lymphocytes play an additional key pathogenic role. It appears expression of plasma membrane bound immunoglobulin (Ig) molecules that efficiently capture ß-cell antigens allows autoreactive B-lymphocytes bypassing normal tolerance induction processes to be the subset of antigen presenting cells most efficiently activating diabetogenic T-cells. NOD mice transgenically expressing Ig molecules recognizing antigens that are (insulin) or not (hen egg lysozyme; HEL) expressed by ß-cells have proven useful in dissecting the developmental basis of diabetogenic B-lymphocytes. However, these transgenic Ig specificities were originally selected for their ability to recognize insulin or HEL as foreign, rather than autoantigens. Thus, we generated and characterized NOD mice transgenically expressing an Ig molecule representative of a large proportion of naturally occurring islet-infiltrating B-lymphocytes in NOD mice recognizing the neuronal antigen peripherin. Transgenic peripherin autoreactive B-lymphocytes infiltrate NOD pancreatic islets, acquire an activated proliferative phenotype, and potently support accelerated T1D development. These results support the concept of neuronal autoimmunity as a pathogenic feature of T1D, and targeting such responses could ultimately provide an effective disease intervention approach. Diabetes 2016 Jul; 65:1977-87.
Leeth, Caroline M.; Racine, Jeremy; Chapman, Harold D.; Arpa, Berta; Carrillo, Jorge; Carrascal, Jorge; Wang, Qiming; Ratiu, Jeremy; Egia-Mendikute, Leire; Rosell-Mases, Estela; Stratmann, Thomas; Verdaguer, Joan; and Serreze, David V., "B-lymphocytes expressing an immunoglobulin specificity recognizing the pancreatic ß-cell autoantigen peripherin are potent contributors to type 1 diabetes development in NOD mice." (2016). Faculty Research 2016. 159.