Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA 95616, USA.
Cell Immunol. 2011;268(1):16-23. doi: 10.1016/j.cellimm.2011.01.005. Epub 2011 Jan 28.
There are now several murine models of autoimmune cholangitis that have features both similar and distinct from human PBC. One such model, the NOD.c3c4 mouse, manifests portal cell infiltrates, anti-mitochondrial antibodies but also biliary cysts. The biliary cysts are not a component of PBC and not found in the other murine models. To address the immunopathology in these mice, we generated genetically B cell deficient Igμ(-/-) NOD.c3c4 mice and compared the immunopathology of these animals to control B cell sufficient NOD.c3c4 mice. B cell deficient mice demonstrated decreased number of non-B cells in the liver accompanied by reduced numbers of activated natural killer cells. The degree of granuloma formation and bile duct damage were comparable to NOD.c3c4 mice. In contrast, liver inflammation, biliary cyst formation and salivary gland inflammation was significantly attenuated in these B cell deficient mice. In conclusion, B cells play a critical role in promoting liver inflammation and also contribute to cyst formation as well as salivary gland pathology in autoimmune NOD.c3c4 mice, illustrating a critical role of B cells in modulating specific organ pathology and, in particular, in exacerbating both the biliary disease and the sialadenitis.
现在有几种自身免疫性胆管炎的鼠模型，这些模型既有与人类 PBC 相似的特征，也有不同的特征。其中一种模型是 NOD.c3c4 小鼠，它表现出门脉细胞浸润、抗线粒体抗体，但也有胆管囊肿。胆管囊肿不是 PBC 的组成部分，也不存在于其他鼠模型中。为了研究这些小鼠的免疫病理学，我们生成了遗传上缺乏 B 细胞的 Igμ(-/-)NOD.c3c4 小鼠，并将这些动物的免疫病理学与具有足够 B 细胞的对照 NOD.c3c4 小鼠进行了比较。缺乏 B 细胞的小鼠表现出肝脏中非 B 细胞数量减少，同时激活的自然杀伤细胞数量也减少。肉芽肿形成和胆管损伤的程度与 NOD.c3c4 小鼠相当。相比之下，这些缺乏 B 细胞的小鼠的肝脏炎症、胆管囊肿形成和唾液腺炎症明显减轻。总之，B 细胞在促进肝脏炎症以及胆管囊肿形成和唾液腺病理学方面发挥着关键作用，说明了 B 细胞在调节特定器官病理学方面的关键作用，特别是在加剧胆管疾病和唾液腺炎方面。
