SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease

PLoS One. 2021 Dec 22;16(12):e0261656. doi: 10.1371/journal.pone.0261656. eCollection 2021.

Abstract

SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n = 8) or severe (n = 5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG+ B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG+ B cells showed increased expression of markers associated with durable B cell memory, including T-bet and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet+ spike-specific IgG+ B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet+ IgG+ memory B cells decreased to baseline levels. Collectively, our results highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Viral / blood
  • B-Lymphocytes / metabolism
  • Biomarkers / analysis
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • Female
  • Flow Cytometry / methods
  • Hospitalization / trends
  • Humans
  • Immunoglobulin G / blood
  • Immunologic Memory
  • Male
  • Memory B Cells / immunology
  • Memory B Cells / metabolism
  • Middle Aged
  • Receptors, Fc / blood
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism*
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity
  • Severity of Illness Index
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Box Domain Proteins / blood
  • T-Box Domain Proteins / metabolism*

Substances

  • Antibodies, Viral
  • Biomarkers
  • FCRL5 protein, human
  • Immunoglobulin G
  • Receptors, Fc
  • Spike Glycoprotein, Coronavirus
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • spike protein, SARS-CoV-2