Memory B cells targeting SARS-CoV-2 spike protein and their dependence on CD4+ T cell help

Cell Rep. 2021 Jun 29;35(13):109320. doi: 10.1016/j.celrep.2021.109320. Epub 2021 Jun 11.


Memory B cells seem to be more durable than antibodies and thus crucial for the long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we investigate SARS-CoV-2 spike-specific memory B cells and their dependence on CD4+ T cell help in different settings of coronavirus disease 2019 (COVID-19). Compared with severely ill individuals, those who recovered from mild COVID-19 develop fewer but functionally superior spike-specific memory B cells. Generation and affinity maturation of these cells is best associated with IL-21+CD4+ T cells in recovered individuals and CD40L+CD4+ T cells in severely ill individuals. The increased activation and exhaustion of memory B cells observed during COVID-19 correlates with CD4+ T cell functions. Intriguingly, CD4+ T cells recognizing membrane protein show a stronger association with spike-specific memory B cells than those recognizing spike or nucleocapsid proteins. Overall, we identify CD4+ T cell subsets associated with the generation of B cell memory during SARS-CoV-2 infection.

Keywords: CD4(+) T cell; CD40L; COVID-19; IL-21; SARS-CoV-2; antibody; memory B cells; recovered; severely ill; spike.

MeSH terms

  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism
  • COVID-19 / immunology*
  • Cross Reactions
  • Humans
  • Immunologic Memory
  • Interleukins / immunology
  • Interleukins / metabolism
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology*


  • Antibodies, Viral
  • Interleukins
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • CD40 Ligand
  • interleukin-21