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

  1. F. Susan Wong1,
  2. Li Wen2,
  3. Michelle Tang3,
  4. Murugappan Ramanathan3,
  5. Irene Visintin3,
  6. Joanne Daugherty3,
  7. Lynn G. Hannum3,
  8. Charles A. Janeway, Jr3 and
  9. Mark J. Shlomchik34
  1. 1Department of Pathology and Microbiology, University of Bristol, Bristol, U.K
  2. 2Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut
  3. 3Section of Immunobiology, Yale School of Medicine, New Haven, Connecticut
  4. 4Department of Laboratory Medicine, Yale School of Medicine, New Haven, Connecticut
  1. Address correspondence and reprint requests to F. Susan Wong, Department of Pathology and Microbiology, University of Bristol, University Walk, Bristol BS8 1TD, U.K. E-mail: susan.wong{at}


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.


  • Dr. Charles A. Janeway, Jr., sadly passed away before the submission of this manuscript. He fully endorsed the work and contents of this study.

    • Accepted July 16, 2004.
    • Received September 22, 2003.
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