High-affinity, neutralizing antibodies to SARS-CoV-2 can be made in the absence of T follicular helper cells [preprint]
UMass Chan AffiliationsDepartment of Pathology
T follicular helper (Tfh) cells
germinal center (GC)-based antiviral antibody responses
B cell responses
Immunology of Infectious Disease
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AbstractT follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 as well as influenza A virus. Tfh-independent responses were mediated by a population we call lymph node (LN)-Th1 cells, which remain in the LN and interact with B cells outside of GCs to promote high-affinity but broad-spectrum antibodies. Strikingly, antibodies generated in the presence and absence of Tfh cells displayed similar neutralization potency against homologous SARS-CoV-2 as well as the B.1.351 variant of concern. These data support a new paradigm for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GCs and even compensate for GCs damaged by viral inflammation.
bioRxiv 2021.06.10.447982; doi: https://doi.org/10.1101/2021.06.10.447982. Link to preprint on bioRxiv.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/29825
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Full author list omitted for brevity. For the full list of authors, see article.
Now published in Science Immunology, doi: https://doi.org/10.1126/sciimmunol.abl5652
RightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.