Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth
Year: 2026
Type: article
Abstract: The cellular, immunogenetic, and antigenic factors affecting the breadth of viral antigen variants recognized by human antibody responses are poorly defined. We developed highly multiplexed panels of DNA-tagged SARS-CoV-2 antigens from up to 20 viral variants to label and sort 6,262 antigen-binding circulating B cells from previously naive mRNA vaccinees or infected patients, and from deceased organ donor lymphoid tissues, to enable antigen receptor and transcriptome sequencing. Atypical B cells and a subset of class-switched memory cells with evidence of recent germinal center exposure were enriched for antigen binding. In contrast to atypical B cells, post-germinal center B cells showed progressively increasing variant binding breadth and somatic hypermutation over time. Vaccination, compared with infection, preferentially stimulated B cells expressing antibodies with inherently high antigen-binding breadth. This large-scale analysis reveals key determinants of antigen-binding breadth, critical for understanding responses to viral infection and guiding vaccine development against rapidly mutating viruses.
Source: Immunity
Authors: Oliver F. Wirz, Prasanti Kotagiri, Emily Haraguchi, Katharina Röltgen, Molly Hunter, Erin Craig, Jumana Afaghani, Ji-Yeun Lee, Sandra C.A. Nielsen, Ramona A. Hoh, Taylor Pursell, Prabhu S. Arunachalam, Monali Manohar, Iris Chang, Jackson P. Schuetz, Brandon Lam, Andrea Fernandes, Evan Do, Donna Smith, Brian Ha, Linda Liao, Javaria Najeeb, Ana R. Otrelo-Cardoso, Chandler Ho, Jacob N. Wohlstadter, George B. Sigal, Theodore S. Jardetzky, Stuart A. Scott, Sean Van Slyck, Mark M. Davis, Bali Pulendran, Jeremy Minshull, Benjamin A. Pinsky, Kari C. Nadeau, Claus U. Niemann, Fan Yang, Scott D. Boyd
Institutions: Stanford Medicine, Stanford University, Monash University, Swiss Tropical and Public Health Institute, University of Basel, ATUM (United States), Stanford Health Care, Meso Scale Discovery (United States), Beth Israel Deaconess Medical Center, Harvard University, Beth Israel Deaconess Hospital, University of California, San Francisco, Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Awards: Mechanisms and Duration of Immunity to SARS-CoV-2, Storage and recall of human B cell memory of influenza over tissues and time, System Biological Analyses of Innate and Adaptive Responses to Vaccination, Effects of aging on primary and secondary vaccine responses in a 15-year longitudinal cohort, Vaccine and Infection Induced Immunity in the Young and Aged
OpenAlex ID: W7147725676