Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19

Cell. 2020 Oct 1;183(1):143-157.e13. doi: 10.1016/j.cell.2020.08.025. Epub 2020 Aug 19.

Abstract

Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiation together with an increase in T-bet+ TH1 cells and aberrant extra-follicular TNF-α accumulation. Parallel peripheral blood studies revealed loss of transitional and follicular B cells in severe disease and accumulation of SARS-CoV-2-specific "disease-related" B cell populations. These data identify defective Bcl-6+ TFH cell generation and dysregulated humoral immune induction early in COVID-19 disease, providing a mechanistic explanation for the limited durability of antibody responses in coronavirus infections, and suggest that achieving herd immunity through natural infection may be difficult.

Keywords: COVID-19; SARS-CoV-2; T follicular helper cells; TNF-α; cytokine dysregulation; double-negative B cells; extra-follicular B cells; germinal centers; humoral immunity; plasmablasts.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • B-Lymphocytes / immunology
  • Coronavirus Infections / immunology*
  • Female
  • Germinal Center / immunology*
  • Germinal Center / pathology
  • Humans
  • Male
  • Middle Aged
  • Pandemics
  • Pneumonia, Viral / immunology*
  • Proto-Oncogene Proteins c-bcl-6 / genetics
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • BCL6 protein, human
  • Proto-Oncogene Proteins c-bcl-6
  • Tumor Necrosis Factor-alpha

Supplementary concepts

  • COVID-19