Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine.

Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine.
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DOI:
10.1016/j.celrep.2023.112780
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发表时间:
2023-07-25
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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疫苗接种后的保护性免疫是由长寿的抗体分泌细胞和静止的记忆B细胞(MBCs)维持的。通过多模式单细胞分析,纵向评估了三名感染ı伊夫的人对两剂SARS-CoV-2mRNA-1273疫苗的反应。分离的成浆细胞和SPEKE+(S-2P+)和S-2P−B细胞的表面蛋白、转录组和B细胞受体的综合分析表明S-2P+细胞之间存在克隆性扩增和累积突变。这些细胞富含在一簇表达免疫球蛋白G的MBCs中,并沿着植根于CXCR3+MBCs的分叉轨迹进化。在12个进化的S-2P+克隆中,有几个克隆早期为浆母细胞,后期为CD71+活化和静止的多核细胞,并表现为队列内和/或队列间的BCR收敛。这些关系表明了SARS-CoV-2疫苗产生的多核细胞的协调和可预测的进化。使用多组单细胞分析,Assis等人。显示了一条涉及浆母细胞和激活的和静止的记忆B细胞的协调轨迹,以响应最初的SARS-CoV-2mRNA疫苗。SPEK特异性BCR曲目分析显示,在6个月的研究期间,亲和力逐渐成熟,并揭示了研究参与者和其他队列中趋同的证据。
Protective immunity following vaccination is sustained by long-lived antibody-secreting cells and resting memory B cells (MBCs). Responses to two-dose SARS-CoV-2 mRNA-1273 vaccination are evaluated longitudinally by multimodal single-cell analysis in three infection-naıïve individuals. Integrated surface protein, transcriptomics, and B cell receptor (BCR) repertoire analysis of sorted plasmablasts and spike+ (S-2P+) and S-2P− B cells reveal clonal expansion and accumulating mutations among S-2P+ cells. These cells are enriched in a cluster of immunoglobulin G-expressing MBCs and evolve along a bifurcated trajectory rooted in CXCR3+ MBCs. One branch leads to CD11c+ atypical MBCs while the other develops from CD71+ activated precursors to resting MBCs, the dominant population at month 6. Among 12 evolving S-2P+ clones, several are populated with plasmablasts at early timepoints as well as CD71+ activated and resting MBCs at later timepoints, and display intra- and/or inter-cohort BCR convergence. These relationships suggest a coordinated and predictable evolution of SARS-CoV-2 vaccine-generated MBCs. Using multiomic single-cell analyses, Assis et al. show a coordinated trajectory involving plasmablasts and activated and resting memory B cells in response to primary SARS-CoV-2 mRNA vaccination. Spike-specific BCR repertoire analysis shows incremental affinity maturation across the 6-month study period and reveals evidence of convergence among study participants and other cohorts.
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