Serreze D V, Chapman H D, Varnum D S, Hanson M S, Reifsnyder P C, Richard S D, Fleming S A, Leiter E H, Shultz L D
The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
J Exp Med. 1996 Nov 1;184(5):2049-53. doi: 10.1084/jem.184.5.2049.
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.
在胰岛素依赖型糖尿病（IDDM）的非肥胖糖尿病（NOD）小鼠模型中，介导胰腺β细胞自身免疫性破坏的T淋巴细胞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，目前尚不清楚APC的哪些特定亚群（B淋巴细胞、巨噬细胞和树突状细胞）在NOD小鼠中促成致糖尿病T细胞的发育和激活。在本研究中，我们利用功能失活的免疫球蛋白（Ig）μ等位基因（Igμ缺失）来培育一种“快速同源”的B淋巴细胞缺陷型NOD小鼠品系，这些小鼠的连锁标记已固定，可界定先前确定的糖尿病易感性（Idd）基因。这些B淋巴细胞缺陷型NOD.Igμ缺失小鼠的T细胞数量正常，但没有明显的IDDM，且对胰岛炎有抵抗力，而B淋巴细胞完整的分离后代中的疾病发生率与我们群体中的标准NOD小鼠相当。因此，B淋巴细胞发挥了一种迄今为止未被认识到的作用，这对NOD小鼠中β细胞自身反应性T细胞的初始发育和/或激活至关重要。
