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

Jackson S. Turner, Julian Q. Zhou, Julianna Han, Aaron J. Schmitz, Amena A. Rizk, Wafaa B. Alsoussi, Tingting Lei, Mostafa Amor, Katherine M. McIntire, Philip Meade, Shirin Strohmeier, Rafael I. Brent, Sara T. Richey, Alem Haile, Yuhe R. Yang, Michael K. Klebert, Teresa Suessen, Sharlene Teefey, Rachel M. Presti, Florian Krammer, Steven H. Kleinstein, Andrew B. Ward and Ali H. Ellebedy ()
Additional contact information
Jackson S. Turner: Washington University School of Medicine
Julian Q. Zhou: Yale University
Julianna Han: The Scripps Research Institute
Aaron J. Schmitz: Washington University School of Medicine
Amena A. Rizk: Washington University School of Medicine
Wafaa B. Alsoussi: Washington University School of Medicine
Tingting Lei: Washington University School of Medicine
Mostafa Amor: Washington University School of Medicine
Katherine M. McIntire: Washington University School of Medicine
Philip Meade: Icahn School of Medicine at Mount Sinai
Shirin Strohmeier: Icahn School of Medicine at Mount Sinai
Rafael I. Brent: Washington University School of Medicine
Sara T. Richey: The Scripps Research Institute
Alem Haile: Washington University School of Medicine
Yuhe R. Yang: The Scripps Research Institute
Michael K. Klebert: Washington University School of Medicine
Teresa Suessen: Washington University School of Medicine
Sharlene Teefey: Washington University School of Medicine
Rachel M. Presti: Washington University School of Medicine
Florian Krammer: Icahn School of Medicine at Mount Sinai
Steven H. Kleinstein: Yale University
Andrew B. Ward: The Scripps Research Institute
Ali H. Ellebedy: Washington University School of Medicine

Nature, 2020, vol. 586, issue 7827, 127-132

Abstract: 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 plasmablasts1–3. This recall response contributes to ‘original antigenic sin’—the selective increase of antibody species elicited by previous exposures to influenza virus antigens4. 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 occur5. 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.

Date: 2020
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DOI: 10.1038/s41586-020-2711-0

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