Research Paper Volume 15, Issue 18 pp 9250—9274
High-throughput single-cell profiling of B cell responses following inactivated influenza vaccination in young and older adults
- 1 Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06510, USA
- 2 Department of Immunobiology, Yale School of Medicine, New Haven, CT 06510, USA
- 3 Section of Infectious Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06510, USA
- 4 Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA
Received: November 16, 2022 Accepted: May 3, 2023 Published: June 26, 2023
https://doi.org/10.18632/aging.204778How to Cite
Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Seasonal influenza contributes to a substantial disease burden, resulting in approximately 10 million hospital visits and 50 thousand deaths in a typical year in the United States. 70 - 85% of the mortality occurs in people over the age of 65. Influenza vaccination is the best protection against the virus, but it is less effective for the elderly, which may be in part due to differences in the quantity or type of B cells induced by vaccination. To investigate this possibility, we sorted pre- and post-vaccination peripheral blood B cells from three young and three older adults with strong antibody responses to the inactivated influenza vaccine and employed single-cell technology to simultaneously profile the gene expression and the B cell receptor (BCR) of the B cells. Prior to vaccination, we observed a higher somatic hypermutation frequency and a higher abundance of activated B cells in older adults than in young adults. Following vaccination, young adults mounted a more clonal response than older adults. The expanded clones included a mix of plasmablasts, activated B cells, and resting memory B cells in both age groups, with a decreased proportion of plasmablasts in older adults. Differential abundance analysis identified additional vaccine-responsive cells that were not part of expanded clones, especially in older adults. We observed broadly consistent gene expression changes in vaccine-responsive plasmablasts and greater heterogeneity among activated B cells between age groups. These quantitative and qualitative differences in the B cells provide insights into age-related changes in influenza vaccination response.