The BB rat

Mordes, John P.; Desemone, James; Rossini, Aldo A.

doi:10.1002/dmr.5610030307

Cited by 157 publications

(71 citation statements)

References 114 publications

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“…However, studies using the nonobese diabetic (NOD) mouse and Bio-breeding rat models have demonstrated that T1D is primarily mediated by T cells (2,3). Thus, it was surprising to find that NOD mice rendered deficient in B cells, either through introduction of an Ig H chain knockout (Ig null ) (4) or treatment with anti-IgM Abs (5), were markedly T1D resistant.…”

Section: B Cell Selection Defects Underlie the Development Of Diabetomentioning

confidence: 99%

B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice

Silveira

Dombrowsky

Johnson

et al. 2004

The Journal of Immunology

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One mechanism whereby B cells contribute to type 1 diabetes in nonobese diabetic (NOD) mice is as a subset of APCs that preferentially presents MHC class II-bound pancreatic β cell Ags to autoreactive CD4 T cells. This results from their ability to use cell surface Ig to specifically capture β cell Ags. Hence, we postulated a diabetogenic role for defects in the tolerance mechanisms normally blocking the maturation and/or activation of B cells expressing autoreactive Ig receptors. We compared B cell tolerance mechanisms in NOD mice with nonautoimmune strains by using the IgHEL and Ig3-83 transgenic systems, in which the majority of B cells recognize one defined Ag. NOD- and nonautoimmune-prone mice did not differ in ability to delete or receptor edit B cells recognizing membrane-bound self Ags. However, in contrast to the nonautoimmune-prone background, B cells recognizing soluble self Ags in NOD mice did not undergo partial deletion and were also not efficiently anergized. The defective induction of B cell tolerance to soluble autoantigens is most likely responsible for the generation of diabetogenic APC in NOD mice.

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Section: B Cell Selection Defects Underlie the Development Of Diabetomentioning

confidence: 99%

B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice

Silveira

Dombrowsky

Johnson

et al. 2004

The Journal of Immunology

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“…As in human IDDM, the pathogenesis of disease in the diabetes prone BB rat is via an autoimmune process characterized by lymphocytic infiltration of the islets [1] and by the presence of serum anti-islet cytotoxic antibodies [2]. Unlike human IDDM, lymphopenia [3] and immune deficiencies [4,5] are found in the BB rat. In both the BB rat and NOD (non-obese diabetic) mouse, another well studied animal model of spontaneous diabetes that shares many immunologic and pathologic features of human IDDM, depressed regulatory T-cell activity is hypthesized to play an important pathogenetic role [3,6].…”

Section: Introductionmentioning

confidence: 99%

“…Unlike human IDDM, lymphopenia [3] and immune deficiencies [4,5] are found in the BB rat. In both the BB rat and NOD (non-obese diabetic) mouse, another well studied animal model of spontaneous diabetes that shares many immunologic and pathologic features of human IDDM, depressed regulatory T-cell activity is hypthesized to play an important pathogenetic role [3,6]. Polyinosinic polycytidylic acid (poly I:C), an inducer of cytokines, increases suppressor T-cell activity and inhibits the development of diabetes in the NOD mouse [7].…”

Section: Introductionmentioning

confidence: 99%

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

Sobel

Goyal

Ahvazi

et al. 1998

Journal of Autoimmunity

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“…Diabetes-resistant BB rats (DRBB) were developed from selective breeding from diabetes-prone (DP) forebears and were used as controls (5).…”

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confidence: 99%

Lowering apolipoprotein CIII delays onset of type 1 diabetes

Holmberg

Refai

Höög

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Serum levels of apolipoprotein CIII (apoCIII) are increased in type 1 diabetic patients, and when β cells are exposed to these diabetic sera, apoptosis occurs, an effect abolished by an antibody against apoCIII. We have investigated the BB rat, an animal model that develops a human-like type 1 diabetes, and found that apoCIII was also increased in sera from prediabetic rats. This increase in apoCIII promoted β-cell death. The endogenous levels of apoCIII were reduced by treating prediabetic animals with an antisense against this apolipoprotein, resulting in a significantly delayed onset of diabetes. ApoCIII thus serves as a diabetogenic factor, and intervention with this apolipoprotein in the prediabetic state can arrest disease progression. These findings suggest apoCIII as a target for the treatment of type 1 diabetes.W e have previously shown that there is a group of patients with type 1 diabetes (T1D) whose sera induce an increased activity of voltage-gated Ca 2+ channels in pancreatic β cells, resulting in increased cytoplasmic free Ca 2+ concentration ([Ca 2+ ] i ) and apoptosis (1). T1D serum was found to contain increased concentrations of apolipoprotein CIII (apoCIII), and we could later demonstrate that this serum factor was responsible for the [Ca 2+ ] i increase and β-cell death in vitro (2). Consequently, the effects of both T1D serum and apoCIII on [Ca 2+ ] i and β-cell death are abolished when β cells are coincubated with an antibody against apoCIII (2).To clarify the extent to which apoCIII is also involved in β-cell death in vivo, we have used the animal model diabetes-prone BB rat (DPBB), which spontaneously, at around the age of 60 d, develops T1D that resembles the human form of the disease (3, 4). Diabetes-resistant BB rats (DRBB) were developed from selective breeding from diabetes-prone (DP) forebears and were used as controls (5).This model gives an opportunity to study the impact of prediabetic interventions to prevent or delay onset of the disease. In this study, three prediabetic age groups (40, 50, and 60 d) were investigated both in vitro and in vivo, and we could demonstrate that lowering the endogenous levels of apoCIII by antisense treatment markedly delayed onset of diabetes. ResultsMorphological and Immunohistochemical Characterization. Qualitative morphological analysis showed that pancreas taken from prediabetic rats at the age of 40 d had a lower number of insulincontaining cells than the age-matched controls. The shape of the islets was round to oval with an intact thin layer of collagen around the islets. No inflammation was seen (Fig. 1A). At the age of 50 d, the number of insulin-containing cells did not differ compared with islets from control rats. Islet shape and border did not differ from control rats. No inflammation was seen (Fig. 1B). At 60 d of age, there was a clear decrease in the number of insulin-positive cells. The shape of the islet was irregular, and in some islets, exocrine cells were found. There was no distinct border between the islets and the surroun...

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The BB rat

Cited by 157 publications

References 114 publications

B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice

B Cell Selection Defects Underlie the Development of Diabetogenic APCs in Nonobese Diabetic Mice

Low Dose Poly I:C Prevents Diabetes in the Diabetes Prone BB Rat

Lowering apolipoprotein CIII delays onset of type 1 diabetes

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