Cell
Volume 184, Issue 5, 4 March 2021, Pages 1201-1213.e14
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Article
Maturation and persistence of the anti-SARS-CoV-2 memory B cell response

https://doi.org/10.1016/j.cell.2021.01.050Get rights and content
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Highlights

  • Seasonal coronavirus memory B cells contribute to the early anti-SARS-CoV-2 response

  • Spike-specific memory B cells with a resting phenotype increase up to 6 months

  • Somatic mutations accumulate in SARS-CoV-2-specific memory B cells over time

  • Longitudinal study reveals a temporal switch to anti-RBD neutralizing memory B cells

Summary

Memory B cells play a fundamental role in host defenses against viruses, but to date, their role has been relatively unsettled in the context of SARS-CoV-2. We report here a longitudinal single-cell and repertoire profiling of the B cell response up to 6 months in mild and severe COVID-19 patients. Distinct SARS-CoV-2 spike-specific activated B cell clones fueled an early antibody-secreting cell burst as well as a durable synchronous germinal center response. While highly mutated memory B cells, including pre-existing cross-reactive seasonal Betacoronavirus-specific clones, were recruited early in the response, neutralizing SARS-CoV-2 RBD-specific clones accumulated with time and largely contributed to the late, remarkably stable, memory B cell pool. Highlighting germinal center maturation, these cells displayed clear accumulation of somatic mutations in their variable region genes over time. Overall, these findings demonstrate that an antigen-driven activation persisted and matured up to 6 months after SARS-CoV-2 infection and may provide long-term protection.

Keywords

COVID-19
germinal center
somatic hypermutation
extrafollicular response
plasma cells
neutralizing antibodies
spike protein
RBD
OC43
HKU1

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