Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5

Human B cells immortalized with Epstein-Barr virus upregulate CCR6 and CCR10 and downregulate CXCR4 and CXCR5
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DOI:
10.1128/jvi.76.6.3072-3077.2002
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发表时间:
2002-03-01
影响因子:
5.4
通讯作者:
Yoshie, O
Yoshie, O
中科院分区:
医学2区
文献类型:
--
作者:
Nakayama, T;Fujisawa, R;Yoshie, O

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与外周血静息B细胞相比,EB病毒永生化的B细胞持续高水平表达CCR6和CCR10,低水平表达CXCR4和CXCR5。因此,这些细胞对CCR6和CCR10的配体有强烈的反应,但对CXCR4和CXCR5的配体没有反应。在人EBV阴性B细胞系BJAB中,稳定表达EBNA2上调CCR6,而稳定表达EBNA2和LMP1下调CXCR4。另一方面,EBNA2或LMP1的稳定表达不能诱导BJAB中CCR10的上调或CXCR5的下调。因此,这些变化可能是由于EBV永生化固定了B细胞分化的浆母细胞样阶段。在传染性单核细胞增多症中,EBV感染的B细胞绕过生发中心,聚集在粘膜表面下。EBV相关的机会性淋巴瘤也往往发生在结外部位。这些体内定位的首选部位与EBV永生化B细胞所表现出的趋化因子受体表达的独特特征相一致。
Compared to peripheral blood resting B cells, Epstein-Barr virus (EBV)-immortalized B cells consistently express CCR6 and CCR10 at high levels and CXCR4 and CXCR5 at low levels. Accordingly, these cells vigorously responded to the ligands of CCR6 and CCR10 but not to those of CXCR4 and CXCR5. In a human EBV-negative B-cell line, BJAB, stable expression of EBNA2 upregulated CCR6, while stable expression of EBNA2 as well as LMP1 downregulated CXCR4. On the other hand, upregulation of CCR10 or downregulation of CXCR5 was not induced in BJAB by stable expression of EBNA2 or LMP1. Thus, these changes may be due to a plasmablast-like stage of B-cell differentiation fixed by EBV immortalization. EBV-infected B cells in infectious mononucleosis are known to avoid germinal centers and accumulate under the mucosal surfaces. EBV-associated opportunistic lymphomas also tend to occur in extranodal sites. These preferred sites of in vivo localization are consistent with the unique profile of chemokine receptor expression exhibited by EBV-immortalized B cells.