B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new "speed congenic" stock of NOD.Ig mu null mice.
B lymphocytes are essential for the initiation of T cell-mediated autoimmune diabetes: analysis of a new "speed congenic" stock of NOD.Ig mu null mice.
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DOI：
10.1084/jem.184.5.2049
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发表时间：
1996-11-01
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在胰岛素依赖型糖尿病（insulin-dependent diabetes mellitus，IDDM）的非肥胖糖尿病（nonobese diabetes，NOD）小鼠模型中，T淋巴细胞介导胰腺β细胞的自身免疫性破坏可能是由于造血来源的抗原呈递细胞（APC）的功能缺陷而产生的。然而，尚不清楚APC（B淋巴细胞、巨噬细胞和树突状细胞）的哪些特定亚群有助于NOD小鼠中致糖尿病性T细胞的发育和活化。在目前的研究中，我们利用功能失活的免疫球蛋白（IG）μ等位基因（IG μ null）来产生B淋巴细胞缺陷NOD小鼠的“速度同源”原种，其固定用于描绘先前鉴定的糖尿病易感性（Idd）基因的连锁标记。这些B淋巴细胞NOD.IG μ基因敲除小鼠具有正常数量的T细胞，但没有明显的IDDM和胰岛炎抗性，而B淋巴细胞完整分离物中的疾病频率与我们群体中的标准NOD小鼠相当。因此，B淋巴细胞起着迄今为止未被认识到的作用，其对于NOD小鼠中β细胞自身反应性T细胞的初始发育和/或活化是必需的。
The T lymphocytes mediating autoimmune destruction of pancreatic beta cells in the nonobese diabetic (NOD) mouse model of insulin-dependent diabetes mellitus (IDDM) may be generated due to functional defects in hematopoietically derived antigen-presenting cells (APC). However, it has not been clear which particular subpopulations of APC (B lymphocytes, macrophages, and dendritic cells) contribute to the development and activation of diabetogenic T cells in NOD mice. In the current study we utilized a functionally inactivated immunoglobulin (Ig) mu allele (Ig mu null) to generate a "speed congenic" stock of B lymphocyte-deficient NOD mice that are fixed for linkage markers delineating previously identified diabetes susceptibility (Idd) genes. These B lymphocyte NOD.Ig mu null mice had normal numbers of T cells but were free of overt IDDM and insulitis resistant, while the frequency of disease in the B lymphocyte intact segregants was equivalent to that of standard NOD mice in our colony. Thus, B lymphocytes play a heretofore unrecognized role that is essential for the initial development and/or activation of beta cell autoreactive T cells in NOD mice.