Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Juan Carlos Yam‐Puc(University of Cambridge), Zhaleh Hosseini(University of Cambridge), Emily C. Horner(University of Cambridge), Pehuén Pereyra Gerber(University of Cambridge), Nonantzin Beristain‐Covarrubias(University of Cambridge), Robert M. Hughes(University of Cambridge), Aleksei Lulla(University of Cambridge), Maria Rust(University of Cambridge), Rebecca H. Boston(University of Cambridge), Magda Ali(University of Cambridge), Katrin Fischer(University of Cambridge), Edward Simmons-Rosello(University of Cambridge), Martin O’Reilly(University of Cambridge), Harry Robson(University of Cambridge), Lucy H. Booth(University of Cambridge), Lakmini Kahanawita(University of Cambridge), Andrea Correa-Noguera(Cambridge University Hospitals NHS Foundation Trust), David M. Favara(Cambridge University Hospitals NHS Foundation Trust), Lourdes Ceron‐Gutierrez(Cambridge University Hospitals NHS Foundation Trust), Baerbel Keller(University of Freiburg), Andrew Craxton(University of Cambridge), Georgina S.F. Anderson(University of Cambridge), Xiaoming Sun(University of Cambridge), Anne Elmer(NIHR Wellcome Trust Southampton Clinical Research Facility), Caroline Saunders(NIHR Wellcome Trust Southampton Clinical Research Facility), Areti Bermperi(NIHR Wellcome Trust Southampton Clinical Research Facility), Sherly Jose(NIHR Wellcome Trust Southampton Clinical Research Facility), Nathalie Kingston(Cambridge University Hospitals NHS Foundation Trust), Thomas E. Mulroney(University of Cambridge), Lucia P. G. Piñon(University of Cambridge), Michael A. Chapman(University of Cambridge), Sofia Grigoriadou(Barts Health NHS Trust), Marion MacFarlane(University of Cambridge), Anne E. Willis(University of Cambridge), Kiran Raosaheb Patil(University of Cambridge), Sarah Spencer(University of Cambridge), Emily Staples(University of Cambridge), Klaus Warnatz(University of Freiburg), Matthew Buckland(Barts Health NHS Trust), Florian Hollfelder(University of Cambridge), Marko Hyvönen(University of Cambridge), Rainer Döffinger(Cambridge University Hospitals NHS Foundation Trust), Christine Parkinson(Cambridge University Hospitals NHS Foundation Trust), Sara Lear(Cambridge University Hospitals NHS Foundation Trust), Nicholas J. Matheson(NHS Blood and Transplant), James Thaventhiran(Cambridge University Hospitals NHS Foundation Trust)
Nature Communications
June 27, 2023
10.1038/s41467-023-38810-0
Cited by 44Open Access
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Abstract

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.

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