|Entry||Database: EMDB / ID: EMD-21714|
|Title||Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 0|
|Sample||Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 0|
|Biological species||Homo sapiens (human)|
|Method||single particle reconstruction / negative staining / Resolution: 20 Å|
|Authors||Han J / Ward A / Richey ST / Yang YR|
|Funding support|| United States, 1 items |
|Citation||Journal: Nature / Year: 2020|
Title: Human germinal centres engage memory and naive B cells after influenza vaccination.
Authors: 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 / ...Authors: 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 /
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.
|Validation Report||Summary, Full report, XML, About validation report|
|Structure viewer||EM map: |
Downloads & links
|File||Download / File: emd_21714.map.gz / Format: CCP4 / Size: 15.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 1.98 Å|
|Symmetry||Space group: 1|
CCP4 map header:
-Entire Polyclonal immune complex of Fab binding the side of the head of ...
|Entire||Name: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 0|
Number of components: 1
-Component #1: protein, Polyclonal immune complex of Fab binding the side of the...
|Protein||Name: Polyclonal immune complex of Fab binding the side of the head of H1 HA from serum of participant 11 at day 0|
Recombinant expression: No
|Source||Species: Homo sapiens (human)|
|Source (natural)||Location in cell: PBMC|
|Specimen||Specimen state: Particle / Method: negative staining|
|Sample solution||pH: 7.4|
|Vitrification||Cryogen name: NONE|
-Electron microscopy imaging
Model: Talos Arctica / Image courtesy: FEI Company
|Imaging||Microscope: FEI TALOS ARCTICA|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 25 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Imaging mode: DARK FIELD|
|Specimen Holder||Model: OTHER|
|Camera||Detector: FEI FALCON II (4k x 4k)|
|Processing||Method: single particle reconstruction / Number of projections: 1561|
|3D reconstruction||Resolution: 20 Å / Resolution method: FSC 0.5 CUT-OFF|
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