Wei Chungwen, Anolik Jennifer, Cappione Amedeo, Zheng Bo, Pugh-Bernard Aimee, Brooks James, Lee Eun-Hyung, Milner Eric C B, Sanz Iñaki
Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
J Immunol. 2007 May 15;178(10):6624-33. doi: 10.4049/jimmunol.178.10.6624.
Human memory B cells comprise isotype-switched and nonswitched cells with both subsets displaying somatic hypermutation. In addition to somatic hypermutation, CD27 expression has also been considered a universal memory B cell marker. We describe a new population of memory B cells containing isotype-switched (IgG and IgA) and IgM-only cells and lacking expression of CD27 and IgD. These cells are present in peripheral blood and tonsils of healthy subjects and display a degree of hypermutation comparable to CD27+ nonswitched memory cells. As conventional memory cells, they proliferate in response to CpG DNA and fail to extrude rhodamine. In contrast to other recently described CD27-negative (CD27neg) memory B cells, they lack expression of FcRH4 and recirculate in the peripheral blood. Although CD27neg memory cells are relatively scarce in healthy subjects, they are substantially increased in systemic lupus erythematosus (SLE) patients in whom they frequently represent a large fraction of all memory B cells. Yet, their frequency is normal in patients with rheumatoid arthritis or chronic hepatitis C. In SLE, an increased frequency of CD27neg memory cells is significantly associated with higher disease activity index, a history of nephritis, and disease-specific autoantibodies (anti-dsDNA, anti-Smith (Sm), anti-ribonucleoprotein (RNP), and 9G4). These findings enhance our understanding of the B cell diversification pathways and provide mechanistic insight into the immunopathogenesis of SLE.
人类记忆B细胞包括同种型转换和未转换的细胞，这两个亚群均表现出体细胞超突变。除体细胞超突变外，CD27表达也被认为是一种通用的记忆B细胞标志物。我们描述了一种新的记忆B细胞群体，其包含同种型转换的（IgG和IgA）细胞以及仅表达IgM的细胞，且缺乏CD27和IgD的表达。这些细胞存在于健康受试者的外周血和扁桃体中，其超突变程度与CD27 +未转换的记忆细胞相当。作为传统记忆细胞，它们对CpG DNA产生增殖反应且不能排出罗丹明。与最近描述的其他CD27阴性（CD27neg）记忆B细胞不同，它们缺乏FcRH4的表达并在外周血中再循环。尽管CD27neg记忆细胞在健康受试者中相对稀少，但在系统性红斑狼疮（SLE）患者中它们显著增加，在这些患者中它们经常占所有记忆B细胞的很大一部分。然而，它们在类风湿性关节炎或慢性丙型肝炎患者中的频率是正常的。在SLE中，CD27neg记忆细胞频率增加与更高的疾病活动指数、肾炎病史以及疾病特异性自身抗体（抗双链DNA、抗史密斯（Sm）、抗核糖核蛋白（RNP）和9G4）显著相关。这些发现增强了我们对B细胞多样化途径的理解，并为SLE的免疫发病机制提供了机制性见解。
