B-cells are required for the initiation of insulitis and sialitis in nonobese diabetic mice

Diabetes. 1997 Jun;46(6):941-6. doi: 10.2337/diab.46.6.941.


Nonobese diabetic (NOD) mice spontaneously develop an acute onset of hyperglycemia reminiscent of human type I diabetes. The disease is the end result of a mononuclear cell infiltration of pancreatic islets (insulitis), culminating in the selective destruction of islet beta-cells by autoreactive T-cells. NOD mice also exhibit defects in B-cell tolerance as manifested by the presence of autoantibodies against islet cell autoantigens. Based on the potential ability of B-cells to act as antigen presenting cells, we hypothesized that autoreactive B-cells of NOD mice may be necessary for the activation of islet reactive CD4+ T-cells. In the present study, we utilized an anti-mu antibody to induce in vivo depletion of B-cells and found that B-cell depletion completely abrogates the development of insulitis and sialitis in NOD mice. In contrast, control IgG-treated NOD mice developed insulitis and sialitis by 5 weeks of age. Additionally, the discontinuation of anti-mu chain antibody treatment led to the full restoration of the B-cell pool and the reappearance of insulitis and sialitis. Thus, we conclude that B-cells are a requisite cell population for the genesis of the inflammatory lesions of the islets of Langerhans. This finding suggests that autoreactive B-cells may act as the antigen presenting cells necessary for the initial activation of beta-cell-reactive CD4+ T-cells implicated in the pathogenesis of autoimmune diabetes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • B-Lymphocytes / immunology*
  • CD4 Antigens / immunology
  • CD8 Antigens / immunology
  • Diabetes Mellitus, Type 1 / etiology*
  • Diabetes Mellitus, Type 1 / immunology
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Immune Sera / immunology
  • Immune Sera / pharmacology*
  • Immunoglobulin mu-Chains / immunology
  • Inflammation
  • Islets of Langerhans / immunology
  • Islets of Langerhans / pathology*
  • Islets of Langerhans / ultrastructure
  • Lipopolysaccharides / pharmacology
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Culture Test, Mixed
  • Lymphocyte Depletion
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Rabbits
  • Salivary Glands / immunology
  • Salivary Glands / pathology*
  • Salivary Glands / ultrastructure
  • Spleen / cytology
  • Spleen / immunology


  • CD4 Antigens
  • CD8 Antigens
  • Immune Sera
  • Immunoglobulin mu-Chains
  • Lipopolysaccharides