Affinity-independent memory B cell origin of the early antibody-secreting cell response in naive individuals upon SARS-CoV-2 vaccination.

IF 25.5 1区 医学 Q1 IMMUNOLOGY Immunity Pub Date : 2024-09-10 Epub Date: 2024-08-20 DOI:10.1016/j.immuni.2024.07.023
Zhe Li, Anna Obraztsova, Fuwei Shang, Opeyemi Ernest Oludada, Joshua Malapit, Katrin Busch, Monique van Straaten, Erec Stebbins, Rajagopal Murugan, Hedda Wardemann
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Abstract

Memory B cells (MBCs) formed over the individual's lifetime constitute nearly half of the circulating B cell repertoire in humans. These pre-existing MBCs dominate recall responses to their cognate antigens, but how they respond to recognition of novel antigens is not well understood. Here, we tracked the origin and followed the differentiation paths of MBCs in the early anti-spike (S) response to mRNA vaccination in SARS-CoV-2-naive individuals on single-cell and monoclonal antibody levels. Pre-existing, highly mutated MBCs showed no signs of germinal center re-entry and rapidly developed into mature antibody-secreting cells (ASCs). By contrast, and despite similar levels of S reactivity, naive B cells showed strong signs of antibody affinity maturation before differentiating into MBCs and ASCs. Thus, pre-existing human MBCs differentiate into ASCs in response to novel antigens, but the quality of the humoral and cellular anti-S response improved through the clonal selection and affinity maturation of naive precursors.

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接种非典-CoV-2 疫苗后,天真个体早期抗体分泌细胞反应的亲和性-非依赖性记忆 B 细胞来源。
在人的一生中形成的记忆 B 细胞(MBC)占人体循环 B 细胞库的近一半。这些预先存在的记忆B细胞主导着对其同源抗原的回忆反应,但它们是如何对新抗原的识别做出反应的还不是很清楚。在这里,我们从单细胞和单克隆抗体水平追踪了 MBCs 的起源,并跟踪了它们在 SARS-CoV-2 免疫个体对 mRNA 疫苗接种的早期抗尖峰(S)反应中的分化路径。预先存在的高度突变的 MBC 没有生殖中心再入的迹象,并迅速发育成成熟的抗体分泌细胞(ASCs)。相比之下,尽管S反应性水平相似,但天真B细胞在分化成MBCs和ASCs之前表现出强烈的抗体亲和性成熟迹象。因此,原有的人类 MBC 在对新抗原做出反应时会分化成 ASC,但体液和细胞抗 S 反应的质量会通过天真前体的克隆选择和亲和性成熟得到改善。
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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