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 M. Hughes, Aleksei Lulla, Maria Rust, Rebecca H. Boston, Magda Ali, Katrin Fischer, Edward Simmons-Rosello, Martin O’Reilly, Harry Robson, Lucy H. Booth, Lakmini Kahanawita, Andrea Correa-Noguera, David M. Favara, Lourdes Ceron‐Gutierrez, Baerbel Keller, Andrew Craxton, Georgina S.F. Anderson, Xiaoming Sun, Anne Elmer, Caroline Saunders, Areti Bermperi, Sherly Jose, Nathalie Kingston, Thomas E. Mulroney, Lucia P. G. Piñon, Michael A. Chapman, Sofia Grigoriadou, Marion MacFarlane, Anne E. Willis, Kiran Raosaheb Patil, Sarah Spencer, Emily Staples, Klaus Warnatz, Matthew Buckland, Florian Hollfelder, Marko Hyvönen, Rainer Döffinger, Christine Parkinson, Sara Lear, Nicholas J. Matheson, James Thaventhiran
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.