A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus
A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus
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DOI：
10.4049/jimmunol.178.10.6624
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发表时间：
2007-05-15
影响因子：
4.4
通讯作者：
Sanz, Inaki
中科院分区：
文献类型：
--
作者：
Wei, Chungwen;Anolik, Jennifer;Sanz, Inaki
人记忆B细胞包括同种型转换和非转换细胞，两个亚群均显示体细胞超变。除了体细胞超突变之外，CD 27表达也被认为是通用记忆B细胞标志物。我们描述了一个新的人口的记忆B细胞含有同种型转换（IgG和伊加）和IgM-只有细胞和缺乏表达的CD 27和IgD。这些细胞存在于健康受试者的外周血和扁桃体中，并显示出与CD 27（+）非转换记忆细胞相当的超突变程度。作为传统的记忆细胞，它们响应于CpG DNA而增殖，并且不能挤出罗丹明。与最近描述的其他CD 27阴性（CD 27 neg）记忆B细胞相反，它们缺乏FcRH 4的表达并在外周血中再循环。虽然CD 27阴性记忆细胞在健康受试者中相对稀少，但它们在系统性红斑狼疮（SLE）患者中显著增加，其中它们经常代表所有记忆B细胞的大部分。然而，它们的频率在类风湿性关节炎或慢性丙型肝炎患者中是正常的。在SLE中，CD 27阴性记忆细胞的频率增加与较高的疾病活动指数、肾炎病史和疾病特异性自身抗体（抗dsDNA、抗Smith（Sm）、抗核糖核蛋白（RNP）和9 G4）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。免疫学杂志，2007，178：6624-6633.
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, antiSmith (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. The Joumal of Immunology, 2007,178: 6624-6633.