TY  - JOUR
AU  - Li, Zhe
AU  - Obraztsova, Anna
AU  - Shang, Fuwei
AU  - Oludada, Opeyemi
AU  - Malapit, Joshua
AU  - Busch, Katrin
AU  - van Straaten, Monique
AU  - Stebbins, Erec
AU  - Murugan, Rajagopal
AU  - Wardemann, Hedda
TI  - Affinity-independent memory B cell origin of the early antibody-secreting cell response in naive individuals upon SARS-CoV-2 vaccination.
JO  - Immunity
VL  - 57
IS  - 9
SN  - 1074-7613
CY  - New York, NY
PB  - Elsevier
M1  - DKFZ-2024-01706
SP  - 2191-2201.e5
PY  - 2024
N1  - #EA:D130#LA:D130# / 2024 Sep 10;57(9):2191-2201.e5
AB  - 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.
KW  - SARS-CoV-2 (Other)
KW  - affinity maturation (Other)
KW  - germinal center (Other)
KW  - humoral immunity (Other)
KW  - mRNA vaccination (Other)
KW  - pre-existing memory B cells (Other)
KW  - somatic hypermutation (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39168129
DO  - DOI:10.1016/j.immuni.2024.07.023
UR  - https://inrepo02.dkfz.de/record/292357
ER  -