Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells
Human CD30+ B cells represent a unique subset related to Hodgkin lymphoma cells
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DOI：
10.1172/jci95993
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发表时间：
2018-07-02
影响因子：
15.9
通讯作者：
Kueppers, Ralf
中科院分区：
文献类型：
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作者：
Weniger, Marc A.;Tiacci, Enrico;Kueppers, Ralf
淋巴结生发中心（GC）和滤泡外（EF）区域中极少数B细胞表达CD 30。它们的特异性特征以及与霍奇金淋巴瘤的表达CD 30的霍奇金和里德/斯滕贝格（HRS）细胞的关系尚不清楚，但高度相关，因为许多淋巴瘤患者目前接受抗CD 30免疫毒素治疗。我们对人CD 30（+）B细胞进行了全面分析。表型和IgV基因分析表明，CD 30（+）GC B淋巴细胞代表典型的GC B细胞，CD 30（+）EF B细胞多为GC后B细胞。CD 30（+）GC和EF B细胞的转录组在很大程度上重叠，共享一个强的MYC签名，但分别与常规GC B细胞和记忆B和浆细胞有显著不同。CD 30（+）GC B细胞代表再分化为中心母细胞的MYC+中心细胞; CD 30（+）EF B细胞代表活跃的增殖记忆B细胞。HRS细胞与CD 30（+）B细胞具有典型的转录组模式，表明它们起源于这些淋巴细胞或在淋巴瘤发生过程中获得其特征性特征。通过比较HRS与正常CD 30（+）B细胞，我们重新定义了HRS细胞的异常和疾病特异性特征。HRS细胞中调控基因组稳定性和胞质分裂的基因显著下调可能解释了其基因组不稳定性和多核性。
Very few B cells in germinal centers (GCs) and extrafollicular (EF) regions of lymph nodes express CD30. Their specific features and relationship to CD30-expressing Hodgkin and Reed/Sternberg (HRS) cells of Hodgkin lymphoma are unclear but highly relevant, because numerous patients with lymphoma are currently treated with an anti-CD30 immunotoxin. We performed a comprehensive analysis of human CD30(+) B cells. Phenotypic and IgV gene analyses indicated that CD30(+) GC B lymphocytes represent typical GC B cells, and that CD30(+) EF B cells are mostly post-GC B cells. The transcriptomes of CD30(+) GC and EF B cells largely overlapped, sharing a strong MYC signature, but were strikingly different from conventional GC B cells and memory B and plasma cells, respectively. CD30(+) GC B cells represent MYC+ centrocytes redifferentiating into centroblasts; CD30(+) EF B cells represent active, proliferating memory B cells. HRS cells shared typical transcriptome patterns with CD30(+) B cells, suggesting that they originate from these lymphocytes or acquire their characteristic features during lymphomagenesis. By comparing HRS to normal CD30(+) B cells we redefined aberrant and disease-specific features of HRS cells. A remarkable downregulation of genes regulating genomic stability and cytokinesis in HRS cells may explain their genomic instability and multinuclearity.