Nature Communications (Jun 2023)
Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade
- Juan Carlos Yam-Puc,
- Zhaleh Hosseini,
- Emily C. Horner,
- Pehuén Pereyra Gerber,
- Nonantzin Beristain-Covarrubias,
- Robert Hughes,
- Aleksei Lulla,
- Maria Rust,
- Rebecca Boston,
- Magda Ali,
- Katrin Fischer,
- Edward Simmons-Rosello,
- Martin O’Reilly,
- Harry Robson,
- Lucy H. Booth,
- Lakmini Kahanawita,
- Andrea Correa-Noguera,
- David Favara,
- Lourdes Ceron-Gutierrez,
- Baerbel Keller,
- Andrew Craxton,
- Georgina S. F. Anderson,
- Xiao-Ming Sun,
- Anne Elmer,
- Caroline Saunders,
- Areti Bermperi,
- Sherly Jose,
- Nathalie Kingston,
- Thomas E. Mulroney,
- Lucia P. G. Piñon,
- CITIID-NIHR COVID−19 BioResource Collaboration,
- Michael A. Chapman,
- Sofia Grigoriadou,
- Marion MacFarlane,
- Anne E. Willis,
- Kiran R. Patil,
- Sarah Spencer,
- Emily Staples,
- Klaus Warnatz,
- Matthew S. Buckland,
- Florian Hollfelder,
- Marko Hyvönen,
- Rainer Döffinger,
- Christine Parkinson,
- Sara Lear,
- Nicholas J. Matheson,
- James E. D. Thaventhiran
Affiliations
- Juan Carlos Yam-Puc
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Zhaleh Hosseini
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Emily C. Horner
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Pehuén Pereyra Gerber
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge
- Nonantzin Beristain-Covarrubias
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Robert Hughes
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Aleksei Lulla
- Department of Biochemistry, University of Cambridge
- Maria Rust
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Rebecca Boston
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Magda Ali
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Katrin Fischer
- Department of Biochemistry, University of Cambridge
- Edward Simmons-Rosello
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Martin O’Reilly
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Harry Robson
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Lucy H. Booth
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Lakmini Kahanawita
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Andrea Correa-Noguera
- Department of Oncology, Cambridge University NHS Hospitals Foundation Trust
- David Favara
- Department of Oncology, Cambridge University NHS Hospitals Foundation Trust
- Lourdes Ceron-Gutierrez
- Department of Clinical Immunology, Cambridge University NHS Hospitals Foundation Trust
- Baerbel Keller
- Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Andrew Craxton
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Georgina S. F. Anderson
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Xiao-Ming Sun
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Anne Elmer
- NIHR Cambridge Clinical Research Facility
- Caroline Saunders
- NIHR Cambridge Clinical Research Facility
- Areti Bermperi
- NIHR Cambridge Clinical Research Facility
- Sherly Jose
- NIHR Cambridge Clinical Research Facility
- Nathalie Kingston
- NIHR BioResource, Cambridge University Hospitals NHS Foundation Trust
- Thomas E. Mulroney
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Lucia P. G. Piñon
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- CITIID-NIHR COVID−19 BioResource Collaboration
- Michael A. Chapman
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Sofia Grigoriadou
- Department of Clinical Immunology, Barts Health
- Marion MacFarlane
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Anne E. Willis
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Kiran R. Patil
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Sarah Spencer
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Emily Staples
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- Klaus Warnatz
- Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg
- Matthew S. Buckland
- Department of Clinical Immunology, Barts Health
- Florian Hollfelder
- Department of Biochemistry, University of Cambridge
- Marko Hyvönen
- Department of Biochemistry, University of Cambridge
- Rainer Döffinger
- Department of Clinical Immunology, Cambridge University NHS Hospitals Foundation Trust
- Christine Parkinson
- Department of Oncology, Cambridge University NHS Hospitals Foundation Trust
- Sara Lear
- Department of Clinical Immunology, Cambridge University NHS Hospitals Foundation Trust
- Nicholas J. Matheson
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge
- James E. D. Thaventhiran
- Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge
- DOI
- https://doi.org/10.1038/s41467-023-38810-0
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 14
Abstract
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.
