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Activation Dynamics and Immunoglobulin Evolution of Pre-existing and Newly Generated Human Memory B cell Responses to Influenza Hemagglutinin.
Immunity ( IF 25.5 ) Pub Date : 2019-07-23 , DOI: 10.1016/j.immuni.2019.06.024 Sarah F Andrews 1 , Michael J Chambers 1 , Chaim A Schramm 1 , Jason Plyler 1 , Julie E Raab 1 , Masaru Kanekiyo 1 , Rebecca A Gillespie 1 , Amy Ransier 1 , Sam Darko 1 , Jianfei Hu 1 , Xuejun Chen 1 , Hadi M Yassine 2 , Jeffrey C Boyington 1 , Michelle C Crank 1 , Grace L Chen 1 , Emily Coates 1 , John R Mascola 1 , Daniel C Douek 1 , Barney S Graham 1 , Julie E Ledgerwood 1 , Adrian B McDermott 1
Immunity ( IF 25.5 ) Pub Date : 2019-07-23 , DOI: 10.1016/j.immuni.2019.06.024 Sarah F Andrews 1 , Michael J Chambers 1 , Chaim A Schramm 1 , Jason Plyler 1 , Julie E Raab 1 , Masaru Kanekiyo 1 , Rebecca A Gillespie 1 , Amy Ransier 1 , Sam Darko 1 , Jianfei Hu 1 , Xuejun Chen 1 , Hadi M Yassine 2 , Jeffrey C Boyington 1 , Michelle C Crank 1 , Grace L Chen 1 , Emily Coates 1 , John R Mascola 1 , Daniel C Douek 1 , Barney S Graham 1 , Julie E Ledgerwood 1 , Adrian B McDermott 1
Affiliation
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Vaccine-induced memory B cell responses to evolving viruses like influenza A involve activation of pre-existing immunity and generation of new responses. To define the contribution of these two types of responses, we analyzed the response to H7N9 vaccination in H7N9-naive adults. We performed comprehensive comparisons at the single-cell level of the kinetics, Ig repertoire, and activation phenotype of established pre-existing memory B cells recognizing conserved epitopes and the newly generated memory B cells directed toward H7 strain-specific epitopes. The recall response to conserved epitopes on H7 HA involved a transient expansion of memory B cells with little observed adaptation. However, the B cell response to newly encountered epitopes was phenotypically distinct and generated a sustained memory population that evolved and affinity matured months after vaccination. These findings establish clear differences between newly generated and pre-existing memory B cells, highlighting the challenges in achieving long-lasting, broad protection against an ever-evolving virus.
中文翻译：
已有的和新生成的人类记忆B细胞对流感血凝素的激活动力学和免疫球蛋白进化。
疫苗引起的对正在发展的病毒（如甲型流感）的记忆B细胞反应涉及激活先前存在的免疫力并产生新的反应。为了定义这两种类型的反应的贡献，我们分析了H7N9天真成人对H7N9疫苗接种的反应。我们在动力学，Ig组成和活化表型的单细胞水平上进行了全面的比较，该过程已建立的已有记忆B细胞能够识别保守的抗原决定簇和新产生的针对H7菌株特异性抗原决定簇的记忆B细胞。对H7 HA上保守表位的召回反应涉及记忆B细胞的瞬时扩增，几乎没有观察到的适应性。然而，B细胞对新遇到的表位的反应在表型上是不同的，并产生了持续的记忆种群，这种记忆种群在疫苗接种后数月发展且亲和力成熟。这些发现在新产生的记忆B细胞与先前存在的记忆B细胞之间建立了明显的区别，突显了在实现对不断发展的病毒的长期，广泛保护方面所面临的挑战。
更新日期：2019-07-23
中文翻译：
已有的和新生成的人类记忆B细胞对流感血凝素的激活动力学和免疫球蛋白进化。
疫苗引起的对正在发展的病毒（如甲型流感）的记忆B细胞反应涉及激活先前存在的免疫力并产生新的反应。为了定义这两种类型的反应的贡献，我们分析了H7N9天真成人对H7N9疫苗接种的反应。我们在动力学，Ig组成和活化表型的单细胞水平上进行了全面的比较，该过程已建立的已有记忆B细胞能够识别保守的抗原决定簇和新产生的针对H7菌株特异性抗原决定簇的记忆B细胞。对H7 HA上保守表位的召回反应涉及记忆B细胞的瞬时扩增，几乎没有观察到的适应性。然而，B细胞对新遇到的表位的反应在表型上是不同的，并产生了持续的记忆种群，这种记忆种群在疫苗接种后数月发展且亲和力成熟。这些发现在新产生的记忆B细胞与先前存在的记忆B细胞之间建立了明显的区别，突显了在实现对不断发展的病毒的长期，广泛保护方面所面临的挑战。
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