AI Article Synopsis
- Memory B cells (MBCs) make up nearly half of the B cell population in humans and play a key role in responding to familiar antigens, but their response to new ones is less understood.
- In a study of mRNA vaccination against SARS-CoV-2, highly mutated pre-existing MBCs transformed quickly into antibody-secreting cells without re-entering germinal centers.
- In contrast, naive B cells underwent antibody affinity maturation before developing into MBCs and antibody-secreting cells, indicating that while existing MBCs respond to new antigens, naive cells enhance the quality of the immune response through their maturation process.
Article 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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| http://dx.doi.org/10.1016/j.immuni.2024.07.023 | DOI Listing |
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