High activation levels maintained in receptor-binding domain-specific memory B cells in people with severe coronavirus disease 2019

Money Gupta; Harikrishnan Balachandran; Raymond H Y Louie; Hui Li; David Agapiou; Elizabeth Keoshkerian; Daniel Christ; William Rawlinson; Michael M Mina; Jeffrey J Post; Bernard Hudson; Nicky Gilroy; Pamela Konecny; Adam W Bartlett; Sarah C Sasson; Golo Ahlenstiel; Dominic Dwyer; Andrew R Lloyd; Marianne Martinello; Fabio Luciani; Rowena A Bull; COSIN study group

doi:10.1111/imcb.12607

High activation levels maintained in receptor-binding domain-specific memory B cells in people with severe coronavirus disease 2019

Immunol Cell Biol. 2023 Feb;101(2):142-155. doi: 10.1111/imcb.12607. Epub 2022 Dec 1.

Authors

Money Gupta^{1

2}, Harikrishnan Balachandran^{1

2}, Raymond H Y Louie^{1

2}, Hui Li², David Agapiou², Elizabeth Keoshkerian², Daniel Christ³, William Rawlinson^{1

4}, Michael M Mina⁵, Jeffrey J Post⁶, Bernard Hudson⁷, Nicky Gilroy⁸, Pamela Konecny⁹, Adam W Bartlett^{1

2

10}, Sarah C Sasson², Golo Ahlenstiel¹¹, Dominic Dwyer⁸, Andrew R Lloyd², Marianne Martinello^{2

8

11}, Fabio Luciani^{1

2}, Rowena A Bull^{1

2}; COSIN study group

Affiliations

¹ Faculty of Medicine, School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
² The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
³ Antibody Therapeutics Lab, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁴ Serology and Virology Division, Department of Microbiology, NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW, Australia.
⁵ Northern Beaches Hospital, Frenchs Forest, NSW, Australia.
⁶ Prince of Wales Clinical School, University of New South Wales, Australia, Sydney, NSW, Australia.
⁷ Infectious diseases, Royal North Shore Hospital, Sydney, NSW, Australia.
⁸ Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia.
⁹ St George and Sutherland Clinical School, University of New South Wales, Sydney, Sydney, NSW, Australia.
¹⁰ Sydney Children's Hospital Randwick, Sydney, NSW, Australia.
¹¹ Blacktown Mount Druitt Hospital, Blacktown, NSW, Australia.

Abstract

The long-term health consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are still being understood. The molecular and phenotypic properties of SARS-CoV-2 antigen-specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen-specific memory B-cell (MBC) population has not yet been analyzed to the same degree, but phenotypic analysis suggests differences following recovery from mild or severe coronavirus disease 2019 (COVID-19). Here, we performed single-cell molecular analysis of the SARS-CoV-2 receptor-binding domain (RBD)-specific MBC population in three patients after severe COVID-19 and four patients after mild/moderate COVID-19. We analyzed the transcriptomic and B-cell receptor repertoire profiles at ~2 months and ~4 months after symptom onset. Transcriptomic analysis revealed a higher level of tumor necrosis factor-alpha (TNF-α) signaling via nuclear factor-kappa B in the severe group, involving CD80, FOS, CD83 and TNFAIP3 genes that was maintained over time. We demonstrated the presence of two distinct activated MBCs subsets based on expression of CD80^hi TNFAIP3^hi and CD11c^hi CD95^hi at the transcriptome level. Both groups revealed an increase in somatic hypermutation over time, indicating progressive evolution of humoral memory. This study revealed distinct molecular signatures of long-term RBD-specific MBCs in convalescence, indicating that the longevity of these cells may differ depending on acute COVID-19 severity.

Keywords: CD11c; CD95; RBD; SARS-CoV-2; memory B cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
COVID-19*
Convalescence
Humans
Memory B Cells
SARS-CoV-2

Substances

Antibodies, Viral