Cutting edge: B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice
Cutting edge: B cell specificity contributes to the outcome of diabetes in nonobese diabetic mice
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DOI：
10.4049/jimmunol.167.10.5535
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发表时间：
2001-11-15
影响因子：
4.4
通讯作者：
Thomas, JW
中科院分区：
文献类型：
--
作者：
Hulbert, C;Riseili, B;Thomas, JW
I型糖尿病（TIDM）是一种自身免疫性疾病，其特征在于T细胞介导的胰腺中产生胰岛素的β细胞的破坏。在TIDM的非肥胖糖尿病（NOD）模型中，胰岛炎和糖尿病依赖于B淋巴细胞的存在;然而，对B细胞库中特异性的要求尚不清楚。为了确定Ag特异性B细胞在TIDM中的作用，将具有不同胰岛素结合潜力的VH基因作为H链转基因引入NOD中。VH 125 H链与内源性L链结合产生一个库，其中1-3%的成熟B细胞是胰岛素特异性的，这些小鼠发展为加速型糖尿病。相比之下，NOD小鼠携带类似的转基因，VH 281，与有限的胰岛素结合发展胰岛炎，但保护TIDM。这些数据表明，在B细胞库中的Ag-特异性成分可能会改变TIDM的过程。
Type I diabetes mellitus (TIDM) is an autoimmune disorder characterized by T cell-mediated destruction of insulin-producing beta cells in the pancreas. In the nonobese diabetic (NOD) model of TIDM, insulitis and diabetes are dependent on the presence of B lymphocytes; however, the requirement for specificity within the B cell repertoire is not known. To determine the role of Ag-specific B cells in TIDM, VH genes with different potential for insulin binding were introduced into NOD as H chain transgenes. VH125 H chain combines with endogenous L chains to produce a repertoire in which 1-3% of mature B cells are insulin specific, and these mice develop accelerated diabetes. In contrast, NOD mice harboring a similar transgene, VH281, with limited insulin binding develop insulitis but are protected from TIDM. The data indicate that Ag-specific components in the B cell repertoire may alter the course of TIDM.