High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults.
High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults.
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DOI：
10.18632/aging.204778
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发表时间：
2023-06-26
期刊：
影响因子：
5.2
通讯作者：
Kleinstein, Steven H.
中科院分区：
文献类型：
--
作者：
Wang, Meng;Jiang, Ruoyi;Mohanty, Subhasis;Meng, Hailong;Shaw, Albert C.;Kleinstein, Steven H.
季节性流感造成了巨大的疾病负担，在美国，每年约有1000万人次就诊，5万人死亡。70 - 85%的死亡率发生在65岁以上的人群中。接种流感疫苗是预防流感病毒的最佳方法，但对老年人效果较差，部分原因可能是接种疫苗诱导的B细胞数量或类型不同。为了研究这种可能性，我们对3名年轻人和3名老年人接种灭活流感疫苗前和接种后的外周血B细胞进行了分类，并采用单细胞技术同时分析了B细胞的基因表达和B细胞受体（BCR）。在接种疫苗之前，我们观察到老年人比年轻人有更高的体细胞超突变频率和更高的活化B细胞丰度。接种疫苗后，年轻人比老年人产生更多的克隆反应。扩增的克隆包括两个年龄组的浆母细胞、活化B细胞和静止记忆B细胞的混合物，老年人的浆母细胞比例减少。差异丰度分析发现了额外的疫苗应答细胞，这些细胞不是扩增克隆的一部分，特别是在老年人中。我们观察到疫苗反应性浆母细胞的基因表达变化大致一致，并且在不同年龄组的活化B细胞中存在更大的异质性。B细胞的这些定量和定性差异为流感疫苗应答的年龄相关变化提供了见解。
Seasonal influenza contributes to a substantial disease burden, resulting in approximately 10 million hospital visits and 50 thousand deaths in a typical year in the United States. 70 - 85% of the mortality occurs in people over the age of 65. Influenza vaccination is the best protection against the virus, but it is less effective for the elderly, which may be in part due to differences in the quantity or type of B cells induced by vaccination. To investigate this possibility, we sorted pre- and post-vaccination peripheral blood B cells from three young and three older adults with strong antibody responses to the inactivated influenza vaccine and employed single-cell technology to simultaneously profile the gene expression and the B cell receptor (BCR) of the B cells. Prior to vaccination, we observed a higher somatic hypermutation frequency and a higher abundance of activated B cells in older adults than in young adults. Following vaccination, young adults mounted a more clonal response than older adults. The expanded clones included a mix of plasmablasts, activated B cells, and resting memory B cells in both age groups, with a decreased proportion of plasmablasts in older adults. Differential abundance analysis identified additional vaccine-responsive cells that were not part of expanded clones, especially in older adults. We observed broadly consistent gene expression changes in vaccine-responsive plasmablasts and greater heterogeneity among activated B cells between age groups. These quantitative and qualitative differences in the B cells provide insights into age-related changes in influenza vaccination response.
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影响因子：
32.4
作者：
Goronzy JJ;Weyand CM
通讯作者：
Weyand CM
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
DOI：
10.4049/jimmunol.1900922
发表时间：
2020-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Avey S;Mohanty S;Chawla DG;Meng H;Bandaranayake T;Ueda I;Zapata HJ;Park K;Blevins TP;Tsang S;Belshe RB;Kaech SM;Shaw AC;Kleinstein SH
通讯作者：
Kleinstein SH
影响因子：
17.1
作者：
Jiang N;He J;Weinstein JA;Penland L;Sasaki S;He XS;Dekker CL;Zheng NY;Huang M;Sullivan M;Wilson PC;Greenberg HB;Davis MM;Fisher DS;Quake SR
通讯作者：
Quake SR
影响因子：
64.8
作者：
Turner JS;Zhou JQ;Han J;Schmitz AJ;Rizk AA;Alsoussi WB;Lei T;Amor M;McIntire KM;Meade P;Strohmeier S;Brent RI;Richey ST;Haile A;Yang YR;Klebert MK;Suessen T;Teefey S;Presti RM;Krammer F;Kleinstein SH;Ward AB;Ellebedy AH
通讯作者：
Ellebedy AH