Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD-CD27- Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients
Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD-CD27- Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients
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DOI：
10.4049/jimmunol.1801236
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发表时间：
2019-09-15
影响因子：
4.4
通讯作者：
Somers, Veerle
中科院分区：
文献类型：
--
作者：
Fraussen, Judith;Marquez, Susanna;Somers, Veerle
IgD（-）CD 27（-）双阴性（DN）B细胞具有促炎特征，在一定比例的多发性硬化（MS）患者中异常升高。在这项研究中，DN B细胞的起源和选择特性进行了研究，在MS患者和健康对照（HC）。采用流式细胞术检测48例HC和96例MS患者外周血DN、IgD（-）CD 27（+）类别转换记忆（CSM）和IgD（+）CD 27（-）幼稚B细胞上发育标志物的表达。对HC和MS患者的外周血DN和CSM B细胞进行高通量适应性免疫受体库测序（各n = 3）。HC和MS患者的DN B细胞表现出相似的表型和IG库特征。表型分析表明DN B细胞的成熟状态是低CD 5、CD 10和CD 38表达。DN组CD 95（+）和伊加（+）细胞的比例低于CSM组B细胞。DN B细胞是Ag经历的，如在适应性免疫受体库测序中其IG基因的体细胞超突变所示，尽管它们显示出比CSM B细胞更低的突变负荷。在DN和CSM B细胞之间发现了共享的克隆，尽管>95%的克隆对于每个群体是独特的，并且发现了V（D）J使用和CDR 3理化性质的差异。然而，DN和CSM B细胞通过独特的分化途径发育，大多数DN B细胞代表较早的成熟状态。
IgD(-)CD27(-) double negative (DN) B cells with proinflammatory characteristics are abnormally elevated in a proportion of multiple sclerosis (MS) patients. In this study, the origin and selection characteristics of DN B cells were studied in MS patients and healthy controls (HC). Expression of developmental markers on peripheral blood DN, IgD(-) CD27(+) class-switched memory (CSM) and IgD(+)CD27(-) naive B cells of HC (n = 48) and MS patients (n = 96) was determined by flow cytometry. High-throughput adaptive immune receptor repertoire sequencing was performed on peripheral blood DN and CSM B cells of HC and MS patients (n = 3 each). DN B cells from HC and MS patients showed similar phenotypic and Ig repertoire characteristics. Phenotypic analysis indicated a mature state of DN B cells by low CD5, CD10, and CD38 expression. However, the frequency of CD95(+) and IgA(+) cells was lower in DN versus CSM B cells. DN B cells are Ag experienced, as shown by somatic hypermutation of their Ig genes in adaptive immune receptor repertoire sequencing, although they showed a lower mutation load than CSM B cells. Shared clones were found between DN and CSM B cells, although >95% of the clones were unique to each population, and differences in V(D)J usage and CDR3 physicochemical properties were found. Thus, DN B cells arise in HC and MS patients via a common developmental pathway that is probably linked to immune aging. However, DN and CSM B cells develop through unique differentiation pathways, with most DN B cells representing an earlier maturation state.