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Investigation of the Role of B-Cells in Type 1 Diabetes in the NOD Mouse

F. Susan Wong¹, Li Wen², Michelle Tang³, Murugappan Ramanathan³, Irene Visintin³, Joanne Daugherty³, Lynn G. Hannum³, Charles A. Janeway, Jr^3,, and Mark J. Shlomchik^3,4

¹ Department of Pathology and Microbiology, University of Bristol, Bristol, U.K
² Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut
³ Section of Immunobiology, Yale School of Medicine, New Haven, Connecticut
⁴ Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut

B-cells are important in the development of type 1 diabetes, but their role is not completely defined. Although B-cells produce autoantibodies, these are not thought to be pathogenic; however, their antigen-presenting function is postulated to be critical. To examine the relative importance of these functions of B-cells, we have generated nonobese diabetic (NOD) B-cell–deficient mice that express a transgene encoding a mutant heavy chain immunoglobulin transgene on the cell surface but cannot secrete immunoglobulins (mIgs). This allowed us to dissect the importance of the relative roles of antigen presentation, dissociated from antibody production. We found that the expression of the mIg transgene increased insulitis and the incidence of diabetes compared with transgene-negative NOD B-cell–deficient mice, indicating that the ability to produce antibodies is not necessary for B-cells to have some effect on the development of diabetes. However, diabetes was not restored to the level seen in normal NOD mice. This may relate to reduced ability to activate an islet-specific T-cell repertoire, presumably due to the reduced islet-specific B-cell repertoire. Our results implicate a specific antigen-presenting function for B-cells.

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