Insulin-dependent diabetes mellitus (IDDM) in humans and NOD mice is an autoimmune disease caused by the selective destruction of pancreatic beta cells by autoreactive T lymphocytes. In addition to the well characterized loss of T cell tolerance to islet autoantigens, the presence of anti-islet antibodies highlights a concomitant dysregulation of B cell tolerance to these antigens. The requisite role of B cells in diabetogenesis has recently been established in studies of B cell deficient NOD mice which were found to be diabetes-free. Whether the role of B cells in NOD diabetogenesis is mediated by the islet-reactive B cells and whether this role involves antigen presentation by B cells is unknown. The present application proposes studies focused on elucidating the mechanisms underlying the role of B cells in autoimmune NOD diabetes. Specifically, the contribution of MHC class II mediated antigen presentation by B cells to NOD diabetogenesis will be assessed. Additionally, the contribution of the autoreactive subset of B cells to NOD diabetogenesis will be determined by skewing the B cell repertoire from diabetes associated Ig specificities. Insights into the mechanisms by which B cells contribute to the etiology of autoimmune diabetes will provide the basis for the design of novel strategies for the prevention of IDDM.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK009969-03
Application #
6402561
Study Section
Special Emphasis Panel (ZRG1-IMB (01))
Program Officer
Hyde, James F
Project Start
2001-08-03
Project End
Budget Start
2001-08-03
Budget End
2002-08-02
Support Year
3
Fiscal Year
2001
Total Cost
$47,580
Indirect Cost
Name
University of Pennsylvania
Department
Surgery
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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