Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

Hum Immunol. 2022 Feb;83(2):119-129. doi: 10.1016/j.humimm.2021.10.007. Epub 2021 Nov 4.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient's immunological status and found dramatic changes in the IGH within the patient's immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion, and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones 2-3 weeks after the onset of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34, and IGHV4-39 in COVID-19 patients were more abundant than those of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

Keywords: B-cell receptor repertoire; COVID-19; Clonal expansion; SARS-CoV-2.

MeSH terms

  • Adolescent
  • Adult
  • Aged, 80 and over
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • B-Lymphocytes / immunology*
  • COVID-19 / immunology*
  • Female
  • Humans
  • Immunoglobulin Heavy Chains / immunology
  • Male
  • Middle Aged
  • Receptors, Antigen, B-Cell / immunology*
  • SARS-CoV-2 / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Immunoglobulin Heavy Chains
  • Receptors, Antigen, B-Cell