High-affinity memory B cells induced by SARS-CoV-2 infection produce more plasmablasts and atypical memory B cells than those primed by mRNA vaccines

Cell Rep. 2021 Oct 12;37(2):109823. doi: 10.1016/j.celrep.2021.109823. Epub 2021 Sep 25.


Although both infections and vaccines induce memory B cell (MBC) populations that participate in secondary immune responses, the MBCs generated in each case can differ. Here, we compare SARS-CoV-2 spike receptor binding domain (S1-RBD)-specific primary MBCs that form in response to infection or a single mRNA vaccination. Both primary MBC populations have similar frequencies in the blood and respond to a second S1-RBD exposure by rapidly producing plasmablasts with an abundant immunoglobulin (Ig)A+ subset and secondary MBCs that are mostly IgG+ and cross-react with the B.1.351 variant. However, infection-induced primary MBCs have better antigen-binding capacity and generate more plasmablasts and secondary MBCs of the classical and atypical subsets than do vaccine-induced primary MBCs. Our results suggest that infection-induced primary MBCs have undergone more affinity maturation than vaccine-induced primary MBCs and produce more robust secondary responses.

Keywords: SARS-CoV-2; atypical memory B cell; mRNA vaccine; memory B cell; plasmablast.

MeSH terms

  • Adult
  • Animals
  • Antibodies, Viral / immunology
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / immunology
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 Vaccines / immunology*
  • Cross Reactions / immunology
  • Female
  • HEK293 Cells
  • Humans
  • Immunization / methods
  • Immunologic Memory
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • Plasma Cells / immunology*
  • RNA, Messenger / immunology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Spike Glycoprotein, Coronavirus / immunology
  • Spike Glycoprotein, Coronavirus / metabolism
  • Vaccination / methods
  • Vaccines / immunology


  • Antibodies, Viral
  • COVID-19 Vaccines
  • RNA, Messenger
  • Spike Glycoprotein, Coronavirus
  • Vaccines
  • spike protein, SARS-CoV-2