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

被引:4
作者
Li, Zhe [1 ]
Obraztsova, Anna [1 ,2 ]
Shang, Fuwei [3 ,4 ]
Oludada, Opeyemi Ernest [1 ,2 ,6 ]
Malapit, Joshua [1 ,2 ]
van Straaten, Monique [3 ,5 ]
Stebbins, Erec [5 ]
Murugan, Rajagopal [1 ,7 ]
Wardemann, Hedda [1 ]
机构
[1] German Canc Res Ctr, Cell Immunol B, D-69120 Heidelberg, Germany
[2] Heidelberg Univ, Fac Biosci, D-69120 Heidelberg, Germany
[3] German Canc Res Ctr, Cellular Immunol, D-69120 Heidelberg, Germany
[4] Heidelberg Univ, Fac Med, Dept Anesthesiol, D-69120 Heidelberg, Germany
[5] German Canc Res Ctr, Struct Biol Infect & Immun, D-69120 Heidelberg, Germany
[6] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada
[7] Leiden Univ, Med Ctr, Ctr Infect Dis, NL-2333 ZA Leiden, Netherlands
关键词
MONOCLONAL-ANTIBODIES; HUMORAL IMMUNITY; PROLIFERATION; ACTIVATION; EXPRESSION; SUBSETS;
D O I
10.1016/j.immuni.2024.07.023
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2191 / 2201.e5
页数:17
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