Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19

Nat Immunol. 2020 Dec;21(12):1506-1516. doi: 10.1038/s41590-020-00814-z. Epub 2020 Oct 7.

Abstract

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • Humans
  • Immunophenotyping
  • SARS-CoV-2 / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral

Grant support