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Cutting Edge |
Departments of Medicine, Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232
Type I diabetes mellitus (TIDM) is an autoimmune disorder
characterized by T cell-mediated destruction of insulin-producing 
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,
VH 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.
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