tetano
Editor, Senior Moderator
Nature
. 2020 Aug 31.
doi: 10.1038/s41586-020-2711-0. Online ahead of print.
Human germinal centres engage memory and naive B cells after influenza vaccination
Jackson S Turner[SUP] 1 [/SUP], Julian Q Zhou[SUP] 2 [/SUP], Julianna Han[SUP] 3 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Amena A Rizk[SUP] 1 [/SUP], Wafaa B Alsoussi[SUP] 1 [/SUP], Tingting Lei[SUP] 1 [/SUP], Mostafa Amor[SUP] 1 [/SUP], Katherine M McIntire[SUP] 1 [/SUP], Philip Meade[SUP] 4 5 [/SUP], Shirin Strohmeier[SUP] 4 [/SUP], Rafael I Brent[SUP] 1 [/SUP], Sara T Richey[SUP] 3 [/SUP], Alem Haile[SUP] 6 [/SUP], Yuhe R Yang[SUP] 3 [/SUP], Michael K Klebert[SUP] 6 [/SUP], Teresa Suessen[SUP] 7 [/SUP], Sharlene Teefey[SUP] 7 [/SUP], Rachel M Presti[SUP] 8 [/SUP], Florian Krammer[SUP] 4 [/SUP], Steven H Kleinstein[SUP] 2 9 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Ali H Ellebedy[SUP] 10 11 [/SUP]
Affiliations
Abstract
Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, leading to a transient wave of circulating antibody-secreting plasmablasts[SUP]1-3[/SUP]. This recall response contributes to "original antigenic sin," the selective boosting of antibody specificities from prior exposures to influenza virus antigens[SUP]4[/SUP]. It remains unclear whether such vaccination can also induce germinal centre (GC) reactions in the draining lymph node (LN) where diversification and maturation of recruited B cells can occur[SUP]5[/SUP]. Here we used ultrasound-guided fine needle aspiration to serially sample the draining LNs and investigate the dynamics and specificity of GC B cell responses after influenza vaccination in humans. We show that influenza vaccine-binding GC B cells can be detected as early as 1 week after vaccination. In 3 out of 8 participants, we detected vaccine-binding GC B cells up to 9 weeks after vaccination. Between 12% and 88% of the responding GC B cell clones overlapped with those detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation (SHM) and encoded broadly cross-reactive monoclonal antibodies (mAbs). In contrast, vaccine-induced B cell clones detected only in the GC compartment exhibited significantly lower SHM frequencies and predominantly encoded strain-specific mAbs, suggesting a naive B cell origin. Electron microscopy-based epitope mapping revealed that some of these strain-specific mAbs recognized epitopes that were not targeted by the early plasmablast response. Our results indicate that influenza virus vaccination of humans can elicit a GC reaction to which B cell clones targeting novel epitopes are more likely to be recruited, thereby broadening the spectrum of vaccine-induced protective antibodies against this rapidly mutating pathogen.
. 2020 Aug 31.
doi: 10.1038/s41586-020-2711-0. Online ahead of print.
Human germinal centres engage memory and naive B cells after influenza vaccination
Jackson S Turner[SUP] 1 [/SUP], Julian Q Zhou[SUP] 2 [/SUP], Julianna Han[SUP] 3 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Amena A Rizk[SUP] 1 [/SUP], Wafaa B Alsoussi[SUP] 1 [/SUP], Tingting Lei[SUP] 1 [/SUP], Mostafa Amor[SUP] 1 [/SUP], Katherine M McIntire[SUP] 1 [/SUP], Philip Meade[SUP] 4 5 [/SUP], Shirin Strohmeier[SUP] 4 [/SUP], Rafael I Brent[SUP] 1 [/SUP], Sara T Richey[SUP] 3 [/SUP], Alem Haile[SUP] 6 [/SUP], Yuhe R Yang[SUP] 3 [/SUP], Michael K Klebert[SUP] 6 [/SUP], Teresa Suessen[SUP] 7 [/SUP], Sharlene Teefey[SUP] 7 [/SUP], Rachel M Presti[SUP] 8 [/SUP], Florian Krammer[SUP] 4 [/SUP], Steven H Kleinstein[SUP] 2 9 [/SUP], Andrew B Ward[SUP] 3 [/SUP], Ali H Ellebedy[SUP] 10 11 [/SUP]
Affiliations
- PMID: 32866963
- DOI: 10.1038/s41586-020-2711-0
Abstract
Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, leading to a transient wave of circulating antibody-secreting plasmablasts[SUP]1-3[/SUP]. This recall response contributes to "original antigenic sin," the selective boosting of antibody specificities from prior exposures to influenza virus antigens[SUP]4[/SUP]. It remains unclear whether such vaccination can also induce germinal centre (GC) reactions in the draining lymph node (LN) where diversification and maturation of recruited B cells can occur[SUP]5[/SUP]. Here we used ultrasound-guided fine needle aspiration to serially sample the draining LNs and investigate the dynamics and specificity of GC B cell responses after influenza vaccination in humans. We show that influenza vaccine-binding GC B cells can be detected as early as 1 week after vaccination. In 3 out of 8 participants, we detected vaccine-binding GC B cells up to 9 weeks after vaccination. Between 12% and 88% of the responding GC B cell clones overlapped with those detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation (SHM) and encoded broadly cross-reactive monoclonal antibodies (mAbs). In contrast, vaccine-induced B cell clones detected only in the GC compartment exhibited significantly lower SHM frequencies and predominantly encoded strain-specific mAbs, suggesting a naive B cell origin. Electron microscopy-based epitope mapping revealed that some of these strain-specific mAbs recognized epitopes that were not targeted by the early plasmablast response. Our results indicate that influenza virus vaccination of humans can elicit a GC reaction to which B cell clones targeting novel epitopes are more likely to be recruited, thereby broadening the spectrum of vaccine-induced protective antibodies against this rapidly mutating pathogen.