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 / Ali H Ellebedy /
PubMed 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 ...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. This recall response contributes to 'original antigenic sin'-the selective increase of antibody species elicited by previous exposures to influenza virus antigens. 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. 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.
EMDB-21703: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 4 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21710: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 4 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21714: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21715: Polyclonal immune complex of Fab binding the receptor binding site of H1 HA from serum of participant 11 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21717: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 11 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21719: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 6 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21722: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 11 at day 18 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21723: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 18 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21726: Polyclonal immune complex of Fab binding the receptor binding region of H1 HA from serum of participant 11 at day 18 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21729: Polyclonal immune complex of Fab binding the receptor binding region of H1 HA from serum of participant 11 at day 35 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21730: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 35 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21731: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 11 at day 35 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21733: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 4 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21734: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 4 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21737: Polyclonal immune complex of Fab binding the side of the head of H3 HA from serum of participant 4 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21739: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21741: Polyclonal immune complex of Fab binding the receptor binding region of H1 HA from serum of participant 5 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21745: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21746: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21750: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21751: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 11 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21752: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21754: Polyclonal immune complex of Fab binding the top of the head of H1 HA from serum of participant 11 at day 60 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21757: Monoclonal immune complex of Fab 2B05 from participant 4 at day 5 binding the side of the head of H1 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21758: Monoclonal immune complex of Fab 2C09 from participant 5 at day 28 binding the vestigial esterase domain of H1 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21759: Monoclonal immune complex of Fab 1B08 from participant 5 at day 60 binding the vestigial esterase domain of H1 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21760: Monoclonal immune complex of Fab 4B10 from participant 5 at day 12 binding the vestigial esterase domain of H3 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21761: Monoclonal immune complex of Fab 1B05 from participant 5 at day 28 binding the stem of H3 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21762: Monoclonal immune complex of Fab 1A12 from participant 5 at day 12 binding the stem of H1 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21763: Monoclonal immune complex of Fab 2C11 from participant 4 at day 5 binding the stem of H3 HA Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21765: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 4 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21768: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 4 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21775: Polyclonal immune complex of Fab binding the vestigial esterase of H3 HA from serum of participant 4 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21776: Polyclonal immune complex of Fab binding the stem of H3 HA from serum of participant 4 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21777: Polyclonal immune complex of Fab binding the stem of H3 HA from serum of participant 4 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21778: Polyclonal immune complex of Fab binding the vestigial esterase of H3 HA from serum of participant 4 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21779: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 4 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21780: Polyclonal immune complex of Fab binding the stem of H3 HA from serum of participant 4 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21781: Polyclonal immune complex of Fab binding the vestigial esterase of H3 HA from serum of participant 4 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21782: Polyclonal immune complex of Fab binding the side of the head of H3 HA from serum of participant 4 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21783: Polyclonal immune complex of Fab binding the receptor binding site of H3 HA from serum of participant 4 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21784: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21785: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21786: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21787: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21788: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21789: Polyclonal immune complex of Fab binding the stem of H1 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21790: Polyclonal immune complex of Fab binding the stem of H3 HA from serum of participant 5 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21791: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21792: Polyclonal immune complex of Fab binding the top of the head of H3 HA from serum of participant 5 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21793: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21794: Polyclonal immune complex of Fab binding the stem of H3 HA from serum of participant 5 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21795: Polyclonal immune complex of Fab binding the side of the head of H3 HA from serum of participant 5 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21796: Polyclonal immune complex of Fab binding the top of the head of H3 HA from serum of participant 5 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21797: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 5 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21798: Polyclonal immune complex of Fab binding the top of the head of H3 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21799: Polyclonal immune complex of Fab binding the vestigial esterase of H3 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21800: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21801: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21802: Polyclonal immune complex of Fab binding the stem of H3 HA from serum of participant 5 at day 28 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21803: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 11 at day 0 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21804: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 11 at day 6 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21806: Polyclonal immune complex of Fab binding the receptor binding region of H3 HA from serum of participant 11 at day 18 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21808: Polyclonal immune complex of Fab binding the head of H3 HA from serum of participant 11 at day 35 Method: EM (single particle) / Resolution: 20.0 Å
EMDB-21809: Polyclonal immune complex of Fab binding the vestigial esterase of H1 HA from serum of participant 4 at day 12 Method: EM (single particle) / Resolution: 20.0 Å
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Homo sapiens (human)
unidentified influenza virus
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Homo sapiens (human)
unidentified influenza virus