B CELLS IN AUTOIMMUNE DIABETES

自身免疫性糖尿病中的 B 细胞

• 批准号: 6177207
• 负责人: ANDREW L SINGER
• 金额: $ 5.33万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-03 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6177207
• 关键词: B lymphocyte; MHC class II antigen; NOD mouse; antibody formation; antigen presentation; autoantibody; cellular pathology; genetically modified animals; insulin dependent diabetes mellitus; pathologic process

Insulin-dependent diabetes mellitus (IDDM) in humans and NOD mice is an autoimmune disease caused by the selective destruction of pancreatic beta cells by autoreactive T lymphocytes. In addition to the well characterized loss of T cell tolerance to islet autoantigens, the presence of anti-islet antibodies highlights a concomitant dysregulation of B cell tolerance to these antigens. The requisite role of B cells in diabetogenesis has recently been established in studies of B cell deficient NOD mice which were found to be diabetes-free. Whether the role of B cells in NOD diabetogenesis is mediated by the islet-reactive B cells and whether this role involves antigen presentation by B cells is unknown. The present application proposes studies focused on elucidating the mechanisms underlying the role of B cells in autoimmune NOD diabetes. Specifically, the contribution of MHC class II mediated antigen presentation by B cells to NOD diabetogenesis will be assessed. Additionally, the contribution of the autoreactive subset of B cells to NOD diabetogenesis will be determined by skewing the B cell repertoire from diabetes associated Ig specificities. Insights into the mechanisms by which B cells contribute to the etiology of autoimmune diabetes will provide the basis for the design of novel strategies for the prevention of IDDM.

人类和点头小鼠中胰岛素依赖性糖尿病（IDDM）是一种自身免疫性疾病，是由自身反应性T淋巴细胞选择性破坏胰腺β细胞引起的。 除了表征对胰岛自身抗原的T细胞耐受性的特征性丧失外，抗ISLET抗体的存在还强调了B细胞耐受性对这些抗原的耐受性不体失调。 B细胞在糖尿病发生中的必要作用最近在B细胞缺乏的NOD小鼠的研究中建立了，发现无糖尿病。 B细胞在NOD糖尿病发生中的作用是否是由胰岛反应性B细胞介导的，以及该作用是否涉及B细胞抗原表现，尚不清楚。 本应用提出的研究重点是阐明B细胞在自身免疫性糖尿病中的作用的机制。 具体而言，将评估B细胞II类介导的抗原介绍对糖尿病发生的抗原表现的贡献。 另外，通过偏向于与糖尿病相关的Ig特异性的B细胞库来确定B细胞自动反应性子集对糖尿病发生的贡献。 对B细胞有助于自身免疫性糖尿病病因的机制的见解将为设计IDDM的新型策略设计提供基础。