B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice.
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.
Hulbert
C
C
Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
Riseili
B
B
Rojas
M
M
Thomas
J W
JW
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007328:Insulin / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology; D007700:Kinetics; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic
D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007328:Insulin