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Human germinal centres engage memory and naive B cells after influenza vaccination
Open accessAbstract
Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, which differentiate into a transient wave of circulating antibody-secreting plasmablasts 1-3. This recall response contributes to 'original antigenic sin'-the selective increase of antibody species elicited by previous exposures to influenza virus antigens 4. It remains unclear whether such vaccination can also induce germinal centre reactions in the draining lymph nodes, where diversification and maturation of recruited B cells can occur 5. Here we used ultrasound-guided fine needle aspiration to serially sample the draining lymph nodes and investigate the dynamics and specificity of germinal centre B cell responses after influenza vaccination in humans. Germinal centre B cells that bind to influenza vaccine could be detected as early as one week after vaccination. In three out of eight participants, we detected vaccine-binding germinal centre B cells up to nine weeks after vaccination. Between 12% and 88% of the responding germinal centre B cell clones overlapped with B cells detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation and encoded broadly cross-reactive monoclonal antibodies. By contrast, vaccine-induced B cell clones detected only in the germinal centre compartment exhibited significantly lower frequencies of somatic hypermutation and predominantly encoded strain-specific monoclonal antibodies, which suggests a naive B cell origin. Some of these strain-specific monoclonal antibodies recognized epitopes that were not targeted by the early plasmablast response. Thus, influenza virus vaccination in humans can elicit a germinal centre reaction that recruits B cell clones that can target new epitopes, thereby broadening the spectrum of vaccine-induced protective antibodies.
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“The detected plasmablasts were unlikely to be a contaminant of blood, because CD14+ monocyte and/or granulocyte frequencies were below 1% in all FNA samples (well below the 10% threshold that was previously established19)”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [19]
In the citing paper
“Clones related to S-binding monoclonal antibodies had significantly increased mutation frequencies in their immunoglobulin heavy chain variable region (IGHV) genes compared to previously published naive B cells19, particularly those related to monoclonal antibodies that cross-reacted with seasonal betacoronaviruses”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [19]
In the citing paper
“These responses to mRNA vaccination are superior to those seen after seasonal influenza virus vaccination in humans19, in whom haemagglutinin-binding germinal centre B cells were detected in only three out of eight participants.”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [19]
In the citing paper
“These data are consistent with previous findings from seasonal influenza virus vaccination in humans that show that the germinal centre reaction can engage pre-existing memory B cells directed against conserved epitopes as well as naive clones targeting novel epitopes19.”
From SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses (2021) · cites this paper as [19]
In the citing paper
“Furthermore, the germinal centre responses after mRNA vaccination were superior to those seen after the seasonal influenza vaccination in humans204.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [204]
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Metadata
- Authors
- Turner, J. S., Zhou, J. Q., Han, J., Schmitz, A. J., Rizk, A. A., Alsoussi, W. B., Lei, T., Amor, M., McIntire, K. M., Meade, P., Strohmeier, S., Brent, R. I., Richey, S. T., Haile, A., Yang, Y. R., Klebert, M. K., Suessen, T., Teefey, S., Presti, R. M., Krammer, F., Kleinstein, S. H., Ward, A. B., & Ellebedy, A. H.
- Affiliations
- Washington University in St. Louis (US)
- Yale University (US)
- Scripps Research Institute (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Ellebedy, Ali H.
- ORCID
- Turner, Jackson S.
- Zhou, Julian Q.
- Han, Julianna
- Schmitz, Aaron J.
- Alsoussi, Wafaa B.
- Lei, Tingting
- McIntire, Katherine M.
- Meade, Philip
- Strohmeier, Shirin
- Brent, Rafael I.
- Richey, Sara T.
- Yang, Yuhe R.
- Klebert, Michael K.
- Teefey, Sharlene
- Presti, Rachel M.
- Krammer, Florian
- Kleinstein, Steven H.
- Ward, Andrew B.
- Ellebedy, Ali H.
- Venue
- Nature
- Published
- 2020-08-31
- Volume
- 586
- Issue
- 7827
- Pages
- 127-132
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7566073
- OpenAlex
- W3082694457
- Cited by
- 304
- References
- 54
- Citations by year
- 2026: 46 · 2025: 40 · 2024: 53 · 2023: 58 · 2022: 51 · 2021: 50 · 2020: 5
- FWCI
- 29.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (UL1TR000448, UL1TR002345)
- National Cancer Institute (T32CA009547, P30CA091842)
- National Institute of Allergy and Infectious Diseases (HHSN272201400008C), AI117287, R01AI128821, R01AI117287, R01AI104739, AI128821, R01AI104732, R56AI117287, 75N93019C00051, T32AI007244, R21AI139813, U01AI141990, U19AI089992, HHSN 272201400006C)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- influenza vaccination, germinal center, memory B cells, naive B cells, somatic hypermutation, original antigenic sin, plasmablasts, monoclonal antibodies, cross-reactive antibodies, strain-specific antibodies, draining lymph nodes, vaccine-induced antibody response
- MeSH terms
- Adult, Animals, B-Lymphocytes, Clone Cells, Female, Humans, Immunologic Memory, Influenza, Human, Influenza Vaccines, Male, Epitope Mapping, Germinal Center, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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