Department of Pathology
Immunology of Infectious Disease | Infectious Disease | Microbiology | Virus Diseases
T 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.
Immunology, COVID-19, antibodies, T follicular helper (Tfh) cells, germinal center (GC)-based antiviral antibody responses, B cell responses
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DOI of Published Version
bioRxiv 2021.06.10.447982; doi: https://doi.org/10.1101/2021.06.10.447982. Link to preprint on bioRxiv.
Now published in Science Immunology, doi: https://doi.org/10.1126/sciimmunol.abl5652
Chen JS, Uthaman G, Wilen CB, Yale University. (2021). High-affinity, neutralizing antibodies to SARS-CoV-2 can be made in the absence of T follicular helper cells [preprint]. UMass Chan Medical School Faculty Publications. https://doi.org/10.1101/2021.06.10.447982. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/2032
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