Division of Gastroenterology and Hepatology, Nagaoka Red Cross Hospital, Nagaoka, Niigata, Japan.
Hepatology. 2012 Mar;55(3):846-55. doi: 10.1002/hep.24757.
There has been increased interest in the role of B cells in the pathogenesis of primary biliary cirrhosis (PBC). Although the vast majority of patients with this disease have anti-mitochondrial antibodies, there is no correlation of anti-mitochondrial antibody titer and/or presence with disease severity. Furthermore, in murine models of PBC, it has been suggested that depletion of B cells may exacerbate biliary pathology. To address this issue, we focused on a detailed phenotypic characterization of mononuclear cell infiltrates surrounding the intrahepatic bile ducts of patients with PBC, primary sclerosing cholangitis, autoimmune hepatitis, chronic hepatitis C, and graft-versus-host disease, including CD3, CD4, CD8, CD20, CD38, and immunoglobulin classes, as well as double immunohistochemical staining for CD38 and IgM. Interestingly, CD20 B lymphocytes, which are a precursor of plasma cells, were found in scattered locations or occasionally forming follicle-like aggregations but were not noted at the proximal location of chronic nonsuppurative destructive cholangitis. In contrast, there was a unique and distinct coronal arrangement of CD38 cells around the intrahepatic ducts in PBC but not controls; the majority of such cells were considered plasma cells based on their expression of intracellular immunoglobulins, including IgM and IgG, but not IgA. Patients with PBC who manifest this unique coronal arrangement were those with significantly higher titers of anti-mitochondrial antibodies.
These data collectively suggest a role for plasma cells in the specific destruction of intrahepatic bile ducts in PBC and confirm the increasing interest in plasma cells and autoimmunity.
人们对 B 细胞在原发性胆汁性肝硬化(PBC)发病机制中的作用越来越感兴趣。尽管绝大多数患有这种疾病的患者都有抗线粒体抗体,但抗线粒体抗体滴度和/或存在与疾病严重程度并无相关性。此外,在 PBC 的小鼠模型中,有人提出 B 细胞耗竭可能会加重胆管病理。为了解决这个问题,我们专注于对 PBC、原发性硬化性胆管炎、自身免疫性肝炎、慢性丙型肝炎和移植物抗宿主病患者肝内胆管周围的单个核细胞浸润进行详细的表型特征分析,包括 CD3、CD4、CD8、CD20、CD38 和免疫球蛋白类别,以及 CD38 和 IgM 的双重免疫组织化学染色。有趣的是,发现 CD20 B 淋巴细胞(浆细胞的前体)散在存在或偶尔形成滤泡样聚集,但在慢性非化脓性破坏性胆管炎的近端位置未见。相比之下,在 PBC 中,CD38 细胞在肝内胆管周围呈独特而明显的冠状排列,但在对照组中未见;这些细胞中的大多数被认为是浆细胞,因为它们表达细胞内免疫球蛋白,包括 IgM 和 IgG,但不包括 IgA。表现出这种独特冠状排列的 PBC 患者其抗线粒体抗体滴度显著更高。
这些数据共同表明浆细胞在 PBC 中肝内胆管的特异性破坏中起作用,并证实了人们对浆细胞和自身免疫的日益关注。