Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Eur J Immunol. 2020 Sep;50(9):1283-1294. doi: 10.1002/eji.202048838. Epub 2020 Aug 13.

Abstract

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM+ and IgM- plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.

Keywords: B cells; COVID‐19; Coronavirus; SARS‐CoV‐2; Uniform Manifold Approximation and Projection (UMAP); carboxyfluorescein succinimidyl ester CFSE; plasmablasts; principal component analysis (PCA); principal components (PCs).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / blood*
  • Antibodies, Viral / classification
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / virology
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity*
  • C-Reactive Protein / immunology
  • COVID-19
  • Case-Control Studies
  • Cell Proliferation
  • Coronavirus Infections / immunology*
  • Coronavirus Infections / mortality
  • Coronavirus Infections / pathology
  • Coronavirus Infections / virology
  • Cross-Sectional Studies
  • Cytokines / genetics
  • Cytokines / immunology
  • Female
  • Fibrin Fibrinogen Degradation Products / immunology
  • Humans
  • Immunity, Humoral
  • Immunoglobulin Isotypes / blood*
  • Immunologic Memory
  • Lung / immunology*
  • Lung / pathology
  • Lung / virology
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Organ Dysfunction Scores
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Pneumonia, Viral / mortality
  • Pneumonia, Viral / pathology
  • Pneumonia, Viral / virology
  • Primary Cell Culture
  • SARS-CoV-2
  • Severity of Illness Index
  • Survival Analysis

Substances

  • Antibodies, Viral
  • Cytokines
  • Fibrin Fibrinogen Degradation Products
  • Immunoglobulin Isotypes
  • fibrin fragment D
  • C-Reactive Protein