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临床百日咳感染后特定记忆B细胞群体动态变化的年龄相关差异。

Age related differences in dynamics of specific memory B cell populations after clinical pertussis infection.

作者信息

van Twillert Inonge, van Gaans-van den Brink Jacqueline A M, Poelen Martien C M, Helm Kina, Kuipers Betsy, Schipper Maarten, Boog Claire J P, Verheij Theo J M, Versteegh Florens G A, van Els Cécile A C M

机构信息

Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

Department of Statistics, Mathematical Modelling and Data Logistics, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.

出版信息

PLoS One. 2014 Jan 13;9(1):e85227. doi: 10.1371/journal.pone.0085227. eCollection 2014.

Abstract

For a better understanding of the maintenance of immune mechanisms to Bordetella pertussis (Bp) in relation to age, we investigated the dynamic range of specific B cell responses in various age-groups at different time points after a laboratory confirmed pertussis infection. Blood samples were obtained in a Dutch cross sectional observational study from symptomatic pertussis cases. Lymphocyte subpopulations were phenotyped by flowcytometry before and after culture. Memory B (Bmem) cells were differentiated into IgG antibody secreting cells (ASC) by polyclonal stimulation and detected by an ELISPOT assay specific for pertussis antigens pertussis toxin (Ptx), filamentous haemagglutinin (FHA) and pertactin (Prn). Bp antigen specific IgG concentrations in plasma were determined using multiplex technology. The majority of subjects having experienced a clinical pertussis episode demonstrated high levels of both Bp specific IgG and Bmem cell levels within the first 6 weeks after diagnosis. Significantly lower levels were observed thereafter. Waning of cellular and humoral immunity to maintenance levels occurred within 9 months after antigen encounter. Age was found to determine the maximum but not base-line frequencies of Bmem cell populations; higher levels of Bmem cells specific for Ptx and FHA were reached in adults and (pre-) elderly compared to under-fours and schoolchildren in the first 6 weeks after Bp exposure, whereas not in later phases. This age effect was less obvious for specific IgG levels. Nonetheless, subjects' levels of specific Bmem cells and specific IgG were weakly correlated. This is the first study to show that both age and closeness to last Bp encounter impacts the size of Bp specific Bmem cell and plasma IgG levels.

摘要

为了更好地理解与年龄相关的针对百日咳博德特氏菌(Bp)免疫机制的维持情况,我们调查了实验室确诊的百日咳感染后不同时间点各年龄组特异性B细胞反应的动态范围。在一项荷兰横断面观察性研究中,从有症状的百日咳病例获取血样。培养前后通过流式细胞术对淋巴细胞亚群进行表型分析。通过多克隆刺激将记忆B(Bmem)细胞分化为分泌IgG抗体的细胞(ASC),并通过针对百日咳抗原百日咳毒素(Ptx)、丝状血凝素(FHA)和百日咳黏附素(Prn)的ELISPOT试验进行检测。使用多重技术测定血浆中Bp抗原特异性IgG浓度。大多数经历过临床百日咳发作的受试者在诊断后的前6周内显示出高水平的Bp特异性IgG和Bmem细胞水平。此后观察到水平显著降低。抗原接触后9个月内,细胞免疫和体液免疫降至维持水平。发现年龄决定Bmem细胞群体的最大频率而非基线频率;与4岁以下儿童和学童相比,成人和(准)老年人在接触Bp后的前6周内达到更高水平的针对Ptx和FHA的Bmem细胞,而在后期则不然。这种年龄效应在特异性IgG水平上不太明显。尽管如此,受试者的特异性Bmem细胞水平和特异性IgG水平呈弱相关。这是第一项表明年龄和距上次接触Bp的时间都影响Bp特异性Bmem细胞大小和血浆IgG水平的研究。

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