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Cited by 310Influenza Virus Research StudiesT-cell and B-cell ImmunologyImmune responses and vaccinations

The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.

Human germinal centres engage memory and naive B cells after influenza vaccination

Open access
Turner, Jackson S., Zhou, Julian Q., Han, Julianna, Schmitz, Aaron J., Rizk, Amena A., Alsoussi, Wafaa B., Lei, Tingting, Amor, Mostafa, McIntire, Katherine M., Meade, Philip, Strohmeier, Shirin, Brent, Rafael I., Richey, Sara T., Haile, Alem, Yang, Yuhe R., Klebert, Michael K., Suessen, Teresa, Teefey, Sharlene, Presti, Rachel M., Krammer, Florian, Kleinstein, Steven H., Ward, Andrew B., Ellebedy, Ali H.·2020·Nature
DOI 10.1038/s41586-020-2711-0PMC PMC7566073
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Abstract

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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Research works printed but not linked: 2

  1. Francis, T. On the doctrine of original antigenic sin. Proc. Am. Phil. Soc. 104, 572–578 (1953).
  2. Carati, C., Gannon, B. & Piller, N. Anatomy and physiology in relation to compression of the upper limb and thorax. J. Lymphoedema 5, 58–67 (2010).

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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
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2020-08-31
Volume
586
Issue
7827
Pages
127-132
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-020-2711-0
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
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

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