Limited Effector Memory B-Cell Response to Envelope Glycoprotein B During Primary Human Cytomegalovirus Infection.

Limited Effector Memory B-Cell Response to Envelope Glycoprotein B During Primary Human Cytomegalovirus Infection.
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原发性人巨细胞病毒感染期间效应记忆 B 细胞对包膜糖蛋白 B 的反应有限。

DOI:
10.1093/infdis/jiv769
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发表时间:
2016
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
A. Marchant
A. Marchant
中科院分区:
--
文献类型:
--
作者:
N. Dauby;D. Sartori;C. Kummert;S. Lecomte;E. Haelterman;M. Delforge;C. Donner;M. Mach;A. Marchant

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背景 在原发性人巨细胞病毒(HCMV)感染后,与针对被膜蛋白的抗体的产生相比,针对包膜糖蛋白B(g B)的抗体的产生被延迟,并且这可能降低对HCMV传播的控制。 方法 在原发性HCMV感染的孕妇队列中研究了gB特异性和被膜蛋白特异性B细胞的频率和表型。健康成人谁有慢性HCMV感染或最近接种破伤风类毒素(TT)作为对照。 结果 原发性HCMV感染与原发性HCMV感染后gB特异性和皮层蛋白特异性B细胞的高频率和相似频率相关。在初次感染期间,皮层蛋白特异性B细胞表达活化的(CD21(低))记忆B细胞(MBC)表型。TT加强免疫也诱导活化的MBC,表明该亚群的扩增是对蛋白抗原的生理B细胞应答的一部分。相比之下,gB特异性B细胞在原发性和慢性感染期间均具有主要的经典(CD21(+))MBC表型。 结论 在原发性HCMV感染期间,gB特异性免疫球蛋白G(IgG)的延迟产生与具有效应子潜力的MBC的有限诱导相关。HCMV可能干扰中和抗体产生的这种新机制可能代表治疗性免疫的靶点。
BACKGROUND Following primary human cytomegalovirus (HCMV) infection, the production of antibodies against envelope glycoprotein B (gB) is delayed, compared with production of antibodies against tegument proteins, and this likely reduces the control of HCMV dissemination. METHODS The frequency and the phenotype of gB-specific and tegument protein-specific B cells were studied in a cohort of pregnant women with primary HCMV infection. Healthy adults who had chronic HCMV infection or were recently immunized with tetanus toxoid (TT) were included as controls. RESULTS Primary HCMV infection was associated with high and similar frequencies of gB-specific and tegument protein-specific B cells following primary HCMV infection. During primary infection, tegument protein-specific B cells expressed an activated (CD21(low)) memory B-cell (MBC) phenotype. Activated MBCs were also induced by TT booster immunization, indicating that the expansion of this subset is part of the physiological B-cell response to protein antigens. In contrast, gB-specific B cells had a predominant classical (CD21(+)) MBC phenotype during both primary and chronic infections. CONCLUSIONS The delayed production of gB-specific immunoglobulin G (IgG) during primary HCMV infection is associated with a limited induction of MBCs with effector potential. This novel mechanism by which HCMV may interfere with the production of neutralizing antibodies could represent a target for therapeutic immunization.
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