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High activation levels maintained in receptor-binding domain-specific memory B cells in people with severe coronavirus disease 2019.
Gupta, Money; Balachandran, Harikrishnan; Louie, Raymond H Y; Li, Hui; Agapiou, David; Keoshkerian, Elizabeth; Christ, Daniel; Rawlinson, William; Mina, Michael M; Post, Jeffrey J; Hudson, Bernard; Gilroy, Nicky; Konecny, Pamela; Bartlett, Adam W; Sasson, Sarah C; Ahlenstiel, Golo; Dwyer, Dominic; Lloyd, Andrew R; Martinello, Marianne; Luciani, Fabio; Bull, Rowena A.
Affiliation
  • Gupta M; Faculty of Medicine, School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
  • Balachandran H; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Louie RHY; Faculty of Medicine, School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
  • Li H; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Agapiou D; Faculty of Medicine, School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
  • Keoshkerian E; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Christ D; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Rawlinson W; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Mina MM; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Post JJ; Antibody Therapeutics Lab, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
  • Hudson B; Faculty of Medicine, School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
  • Gilroy N; Serology and Virology Division, Department of Microbiology, NSW Health Pathology, Prince of Wales Hospital, Sydney, NSW, Australia.
  • Konecny P; Northern Beaches Hospital, Frenchs Forest, NSW, Australia.
  • Bartlett AW; Prince of Wales Clinical School, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Sasson SC; Infectious diseases, Royal North Shore Hospital, Sydney, NSW, Australia.
  • Ahlenstiel G; Infectious Diseases, Westmead Hospital, Sydney, NSW, Australia.
  • Dwyer D; St George and Sutherland Clinical School, University of New South Wales, Sydney, Sydney, NSW, Australia.
  • Lloyd AR; Faculty of Medicine, School of Medical Sciences, University of New South Wales Australia, Sydney, NSW, Australia.
  • Martinello M; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
  • Luciani F; Sydney Children's Hospital Randwick, Sydney, NSW, Australia.
  • Bull RA; The Kirby Institute, University of New South Wales, Australia, Sydney, NSW, Australia.
Immunol Cell Biol ; 101(2): 142-155, 2023 02.
Article de En | MEDLINE | ID: mdl-36353774
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 CD80hi TNFAIP3hi and CD11chi CD95hi 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.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: COVID-19 Limites: Humans Langue: En Journal: Immunol Cell Biol Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2023 Type de document: Article Pays d'affiliation: Australie

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: COVID-19 Limites: Humans Langue: En Journal: Immunol Cell Biol Sujet du journal: ALERGIA E IMUNOLOGIA Année: 2023 Type de document: Article Pays d'affiliation: Australie