Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving
- Yale School of Medicine, United States
- Washington University School of Medicine, St Louis, United States
- Worcester Polytechnic Institute, United States
- University of Oxford, United Kingdom
Abstract
The poor efficacy of seasonal influenza virus vaccines is often attributed to pre-existing immunity interfering with the persistence and maturation of vaccine-induced B cell responses. We previously showed that a subset of vaccine-induced B cell lineages are recruited into germinal centers (GCs) following vaccination, suggesting that affinity maturation of these lineages against vaccine antigens can occur. However, it remains to be determined whether seasonal influenza vaccination stimulates additional evolution of vaccine-specific lineages, and previous work has found no significant increase in somatic hypermutation (SHM) among influenza-binding lineages sampled from the blood following seasonal vaccination in humans. Here, we investigate this issue using a phylogenetic test of measurable immunoglobulin sequence evolution. We first validate this test through simulations and survey measurable evolution across multiple conditions. We find significant heterogeneity in measurable B cell evolution across conditions, with enrichment in primary response conditions such as HIV infection and early childhood development. We then show that measurable evolution following influenza vaccination is highly compartmentalized: while lineages in the blood are rarely measurably evolving following influenza vaccination, lineages containing GC B cells are frequently measurably evolving. Many of these lineages appear to derive from memory B cells. We conclude from these findings that seasonal influenza virus vaccination can stimulate additional evolution of responding B cell lineages, and imply that the poor efficacy of seasonal influenza vaccination is not due to a complete inhibition of vaccine-specific B cell evolution.
Data availability
The manuscript is a computational study. All data used are publicaly available. Source code are available at https://bitbucket.org/kleinstein/projects.
Article and author information
Author details
Steven H Kleinstein
Funding
National Institute of Allergy and Infectious Diseases (R01 AI104739)
- Steven H Kleinstein
FP7 Ideas: European Research Council (614725-PATHPHYLODYN)
- Oliver G Pybus
National Institute of Allergy and Infectious Diseases (R21 AI139813)
- Dr Ali Ellebedy
National Institute of Allergy and Infectious Diseases (U01 AI141990)
- Dr Ali Ellebedy
National Institute of Allergy and Infectious Diseases (HHSN272201400006C)
- Dr Ali Ellebedy
National Institute of Allergy and Infectious Diseases (5T32CA009547)
- Jackson S Turner
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Hoehn et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Human B cell lineages associated with germinal centers following influenza vaccination are measurably evolving
eLife 10:e70873.
https://doi.org/10.7554/eLife.70873
