Prediabetes pp 53-62 | Cite as

Sites of the Defects Leading to Autoimmunity in the Spontaneously Diabetic BB Rat

  • Joanne Scott
  • David C. Benjamin
  • John C. Herr
  • Victor H. Engelhard
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 246)


Although spontaneous hyperglycemic syndromes have long been recognized in a variety of species, only a very few appear to have an autoimmune pathogenesis. To date, the animal model most closely resembling human Type I diabetes mellitus is the BB rat (1,2, for reviews). The BB rat syndrome is characterized by a sudden onset of severe hyperglycemia associated with ketoacidosis, weight loss, and virtually complete pancreatic beta cell depletion, followed by death within a few days unless insulin is administered. Onset of hyperglycemia occurs in approximately 70 percent of diabetes-prone littermates, usually between 60 and 120 days of age. As in humans, susceptibility to diabetes is associated with the major histocompatibility complex (MHC). The BB rat also exhibits profound T-lymphocytopenia, antedating onset of diabetes and demonstrating a marked decrease in both T-helper/inducer (Th/Ti) and T-cytotoxic/suppressor (TcTs) cell populations. As is typical of autoimmunity in other animals, BB rat l3rniphocytes show depressed responsiveness to concanavalin A (ConA) and to allogeneic stimulator cells in mixed lymphocyte reactions (MLRs). The autoimmune nature of the syndrome in BB rats is evidenced by the presence of an intense mononuclear infiltration of the pancreatic islets (insulitis) and the presence in serum of various autoantibodies, including antibodies directed against surface determinants of islet cells (1,2, for reviews).


Bone Marrow Stem Cell Bone Marrow Chimera Bone Marrow Recipient Neonatal Thymectomy Thymus Graft 
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  1. 1.
    Rossini, A.A., Mordes, J.P., Like, A.A., 1985, Immunology of in- sulin-dependent diabetes mellitus. Ann Rev Immunol 3: 291–322. [Review].CrossRefGoogle Scholar
  2. 2.
    Naji, A., Silvers, W.K., Barker, C.F., 1983, Autoimmunity and Type I (insulin-dependent) diabetes mellitus. Transplantation 36: 355–261. [Review].PubMedCrossRefGoogle Scholar
  3. 3.
    Naji, A., Silvers, W.K., Bellgrau, D., Anderson, A.O., Plotkin, S., Barker, C.F., 1981, Prevention of diabetes in rats by bone marrow transplantation. Ann Surg 194: 328–338.Google Scholar
  4. 4.
    Scott, J., Engelhard, V.H., Curnow, R.T., Benjamin, D.C., 1986, Prevention of diabetes in BB rats. 1. Evidence suggesting a requirement for mature T cells in bone marrow inoculum of neonatally injected rats. Diabetes 35: 1034–1040.PubMedCrossRefGoogle Scholar
  5. 5.
    Scott, J., Engelhard, V.H., Benjamin, D.C., 1987, Bone marrow irradiation chimeras in the BB rat: Evidence suggesting two defects leading to diabetes and lymphopoenia. Diabetologia 30: 774–781.PubMedCrossRefGoogle Scholar
  6. 6.
    Greiner, D.L., Handler, E.S., Nakano, K., Mordes, J.P., Rossini, A.A., 1986, Absence of RT-6 T cell subset in diabetes-prone BB/W rats. J Immunol 135: 148–151.Google Scholar
  7. 7.
    Scott, J., Engelhard, V.H., Benjamin, D.C., 1985, The site of autoimmune defect(s) in the BB rat. Diabetes 34(Suppl. 1): 73A. [Abstract].CrossRefGoogle Scholar
  8. 8.
    Scott, J., Benjamin, D.C., McGill, P., Engelhard, V.H., 1986, Thjnnus transplantation with and without prior thymectomy, in neonatal BB/Ch rats. Diabetes 35(Suppl. 1): 69A. [Abstract]Google Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Joanne Scott
    • 1
    • 2
  • David C. Benjamin
    • 3
  • John C. Herr
    • 4
  • Victor H. Engelhard
    • 3
  1. 1.Departments of PediatricsCancer CenterUSA
  2. 2.Departments of PharmacologyCancer CenterUSA
  3. 3.Departments of MicrobiologyCancer CenterUSA
  4. 4.Anatomy and Cell BiologyCancer CenterUSA

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