Type I diabetes mellitus (TIDM) is an autoimmune disorder characterized by T cell-mediated destruction of insulin-producing beta cells in the pancreas. In the nonobese diabetic (NOD) model of TIDM, insulitis and diabetes are dependent on the presence of B lymphocytes; however, the requirement for specificity within the B cell repertoire is not known. To determine the role of Ag-specific B cells in TIDM, V(H) genes with different potential for insulin binding were introduced into NOD as H chain transgenes. VH125 H chain combines with endogenous L chains to produce a repertoire in which 1-3% of mature B cells are insulin specific, and these mice develop accelerated diabetes. In contrast, NOD mice harboring a similar transgene, VH281, with limited insulin binding develop insulitis but are protected from TIDM. The data indicate that Ag-specific components in the B cell repertoire may alter the course of TIDM.
Pubmed ID: 11698422 RIS Download
Mesh terms: Animals | B-Lymphocytes | Diabetes Mellitus, Type 1 | Disease Progression | Female | Immunoglobulin Heavy Chains | Immunoglobulin M | Immunoglobulin Variable Region | Insulin | Islets of Langerhans | Kinetics | Mice | Mice, Inbred NOD | Mice, Transgenic
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