Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA.
Cell Rep. 2023 Jul 25;42(7):112780. doi: 10.1016/j.celrep.2023.112780. Epub 2023 Jul 12.
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-naïve 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.
接种疫苗后产生的保护性免疫由长寿的抗体分泌细胞和静止记忆 B 细胞（MBC）维持。在三名未感染的个体中，通过多模式单细胞分析对两剂 SARS-CoV-2 mRNA-1273 疫苗接种的反应进行了纵向评估。对分选的浆母细胞和刺突（S-2P）和 S-2P B 细胞进行的表面蛋白、转录组学和 B 细胞受体（BCR）库分析表明，S-2P 细胞中存在克隆扩增和积累突变。这些细胞富集在一群表达免疫球蛋白 G 的 MBC 中，并沿着以 CXCR3 MBC 为根的分叉轨迹进化。一个分支导致 CD11c 非典型 MBC，而另一个分支则从 CD71 激活前体发育为静止 MBC，这是 6 个月时的主要群体。在 12 个不断进化的 S-2P 克隆中，有几个克隆在早期就有浆母细胞，在晚期就有 CD71 激活和静止的 MBC，并且显示出 intra- 和/或 inter-cohort BCR 收敛。这些关系表明 SARS-CoV-2 疫苗产生的 MBC 具有协调和可预测的进化。
