B-cell polyclonal activation and Epstein-Barr viral abortive lytic cycle are two key features in acute infectious mononucleosis

B-cell polyclonal activation and Epstein-Barr viral abortive lytic cycle are two key features in acute infectious mononucleosis
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DOI:
10.1016/j.jcv.2011.05.023
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发表时间:
2011-09-01
影响因子:
8.8
通讯作者:
Vendrell, Jean-Pierre
Vendrell, Jean-Pierre
中科院分区:
医学3区
文献类型:
--
作者:
Al Tabaa, Yassine;Tuaillon, Edouard;Vendrell, Jean-Pierre

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背景资料:急性传染性单核细胞增多症(AIM)通常与大的EBV B细胞储库细胞和强烈的B细胞多克隆活化相关,而在慢性EBV感染的健康对照中,静止的EBV感染的记忆B细胞的数量非常低。为了评价离体B细胞多克隆活化的程度和功能,定量整合在B细胞中的EBV DNA,计算AIM中B细胞和自发分泌EBV抗原的循环B细胞中的功能性EBV DNA库。循环B细胞和分化成浆母细胞和浆细胞的B细胞,对6例AIM患者和7例健康EBV携带者的早期(BZLF 1)和晚期病毒抗原(gp 350)分泌细胞(SC)进行计数。体外B细胞多克隆活化分别诱导8000- 24,000 BZLF 1-和1000-3000 gp 350-SC/10(6)B细胞。这些数据表明,只有11.1-19.5%的表达BZLF 1的细胞合成gp 350,因此完成了EBV裂解周期。此外,反映正在进行的病毒复制的循环自发BZLF 1-和gp 350-SC是罕见的(分别为20-120和10-30/10(6)B细胞),它们的低数量与循环浆细胞的高水平形成对比(CD 19(+)B细胞的1.1-10.2%)。在体内终末B细胞分化为浆细胞可以揭示EBV B细胞库对特异性细胞毒性T细胞的作用。细胞应答并与主要的流产功能-EBV-储库结合,强烈地有助于AIM中细胞EBV储库的快速衰减。(C)2011 Elsevier B. V.保留所有权利。
Background: Acute infectious mononucleosis (AIM) is generally associated with a large EBV B cell reservoir cells and an intense B-cell polyclonal activation whereas the number of quiescent EBV-infected memory B cells in chronically EBV-infected healthy controls is very low.Objectives: To evaluate the extent and functionality of ex vivo B-cell polyclonal activation, quantify the EBV DNA integrated in B cells, enumerate the functional EBV DNA reservoir in B cells and circulating B cells spontaneously secreting EBV antigens in AIM.Study design: Circulating B cells and B cells differentiating into plamablasts and plasma cells, early (BZLF1)- and late viral antigen (gp350)-secreting-cells (SCs) were enumerated in six AIM patients and seven healthy EBV carriers.Results: In vitro B-cell polyclonal activation induced 8000-24,000 BZLF1- and 1000-3000 gp350-SCs/10(6) B cells, respectively. These data suggest that only 11.1-19.5% of cells expressing BZLF1 synthesized gp350 and so completed the EBV-lytic cycle. Furthermore, circulating spontaneous BZLF1- and gp350-SCs that reflect ongoing viral replication were rare (20-120 and 10-30/10(6) B cells, respectively), and their low numbers contrasted with the high levels of circulating plasma cells (1.1-10.2% of CD19(+) B cells).Conclusion: The in vivo terminal-B-cell differentiation into plasma cells could unmask EBV B-cell reservoir to specific cytotoxic T-cell response and combined with a predominant abortive functional-EBV-reservoir, strongly contribute to rapid decay of cellular EBV reservoir in AIM. (C) 2011 Elsevier B.V. All rights reserved.