德国癌症研究中心Hedda Wardemann等研究人员合作揭示，SARS-CoV-2疫苗初次接种者中早期抗体分泌细胞反应中的抗原亲和力非依赖记忆B细胞的起源。该研究于2024年8月20日在线发表于国际一流学术期刊《免疫》。

研究人员跟踪了在SARS-CoV-2疫苗接种后对抗S（刺突）抗原的早期反应中，记忆B细胞（MBC）在单细胞和单克隆抗体水平的来源和分化路径。研究人员发现，预先存在的高度突变的MBC没有表现出重新进入生发中心的迹象，而是迅速发展为成熟的抗体分泌细胞（ASC）。

相比之下，尽管S抗原的反应水平相似，初次接触的B细胞在分化成MBC和ASC之前表现出了强烈的抗体亲和力成熟的迹象。因此，预先存在的人类MBC在应对新抗原时分化为ASC，但通过对初次接触的前体细胞的克隆选择和亲和力成熟，体液和细胞的抗S反应质量得到了改善。

据介绍，MBC在个体的生命周期中形成，占据了人类循环B细胞库的近一半。这些先天存在的MBC主导了对其特异性抗原的记忆反应，但它们如何应对新抗原的识别仍不清楚。

附：英文原文

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

Author: Zhe Li, Anna Obraztsova, Fuwei Shang, Opeyemi Ernest Oludada, Joshua Malapit, Katrin Busch, Monique van Straaten, Erec Stebbins, Rajagopal Murugan, Hedda Wardemann

Issue&Volume: 2024-08-20

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.

DOI: 10.1016/j.immuni.2024.07.023

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00372-8