The memory B cell response to influenza vaccination is impaired in older persons.

The memory B cell response to influenza vaccination is impaired in older persons.
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老年人的记忆B细胞对流感疫苗接种的反应受损。

DOI:
10.1016/j.celrep.2022.111613
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发表时间:
2022-11-08
期刊:
影响因子:
8.8
通讯作者:
--
中科院分区:
生物学1区
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流感感染导致与年龄相关的死亡率和发病率增加。最有效的对策是接种疫苗;然而,疫苗在老年人中提供适度的保护。为了研究衰老如何影响记忆B细胞反应,我们通过索引流式分选和单细胞RNA测序(scRNA-seq)在20名接种三价流感疫苗的健康成年人中追踪血凝素特异性B细胞。我们证明了在接种疫苗后6周,记忆B细胞区室中存在年龄相关的偏斜,较年轻的成年人发展出具有FcRL 5+“非典型”表型的血凝素特异性记忆B细胞,显示出体细胞超变和阳性选择的证据,这在老年人中发生的程度较小。我们使用来自配对的人淋巴结和血液样品的公开可用的scRNA-seq来证实FcRL 5+非典型记忆B细胞可以源自生发中心(GC)前体。总之,本研究表明,接种疫苗后的老年人GC反应和记忆B细胞反应是有缺陷的。流感疫苗接种后异质HA特异性记忆B细胞扩增免疫接种后HA + FcRL 5 + B细胞的扩增减少老年人HA+ FcRL 5 + B细胞显示出生殖中心选择的证据老年人中HA+ FcRL 5 + B细胞的阳性选择减少对疫苗接种的免疫应答随着年龄的增长而减弱。Burton等人使用流感疫苗特异性B细胞的单细胞RNA测序和流式细胞术来描述老年人中B细胞记忆产生、抗体突变及其随后选择的变化。
Influenza infection imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how aging impacts the memory B cell response, we track hemagglutinin-specific B cells by indexed flow sorting and single-cell RNA sequencing (scRNA-seq) in 20 healthy adults that were administered the trivalent influenza vaccine. We demonstrate age-related skewing in the memory B cell compartment 6 weeks after vaccination, with younger adults developing hemagglutinin-specific memory B cells with an FcRL5+ “atypical” phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We use publicly available scRNA-seq from paired human lymph node and blood samples to corroborate that FcRL5+ atypical memory B cells can derive from germinal center (GC) precursors. Together, this study shows that the aged human GC reaction and memory B cell response following vaccination is defective. Heterogeneous HA-specific memory B cells expand post influenza vaccination Older people have reduced expansion of HA+FcRL5+ B cells post immunization HA+FcRL5+ B cells show evidence of germinal center selection Positive selection of HA+FcRL5+ B cells is reduced in older individuals Immune responses to vaccination wane with age. Burton et al. used single-cell RNA sequencing and flow cytometry of influenza-vaccine-specific B cells to delineate changes in B cell memory generation, antibody mutation, and their subsequent selection in older persons.
DOI: 10.1016/j.virol.2009.12.003
发表时间: 2010-03-01
期刊: VIROLOGY
影响因子: 3.7
作者:
Chen, Grace L.;Lamirande, Elaine W.;Jin, Hong;Kemble, George;Subbarao, Kanta
通讯作者: Subbarao, Kanta