High-affinity, neutralizing antibodies to SARS-CoV-2 can be made without T follicular helper cells
Year: 2022
Type: article
Abstract: 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. One-Sentence Summary Complementary pathways of antibody production mediate neutralizing responses to SARS-CoV-2.
Source: Science Immunology
Authors: Jennifer S. Chen, Ryan D. Chow, Eric Song, Tianyang Mao, Benjamin Israelow, Kathy Kamath, Joel Bozekowski, Winston A. Haynes, Renata B. Filler, Bridget L. Menasche, Jin Wei, Mia Madel Alfajaro, Wenzhi Song, Lei Peng, Lauren Carter, Jason S. Weinstein, Uthaman Gowthaman, Sidi Chen, Joe Craft, John C. Shon, Akiko Iwasaki, Craig B. Wilen, Stephanie C. Eisenbarth
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Bill and Melinda Gates Foundation, Yale University, Fast Grants, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Advancing Translational Sciences
Awards: Role of virus-receptor interactions in determining norovirus tropism and pathogenesis in vivo, Regulation of T cell-derived cytokines in allergic airway inflammation, G5850682332, Follicular Helper T Cell Function in Autoimmunity, The role of tuft cells in norovirus pathogenesis, Mechanosensation in tumorigenesis and metastasis, Meningeal lymphangiogenesis effect on malignancy ofglioblastoma., Medical Scientist Training Program, Immunohematology/Transfusion Medicine Research Training, Immune Responses in Lupus, Interdisciplinary Immunology Training Program, Immune Mechanisms Regulating Allergy, Yale Clinical and Translational Science Award, Training in Investigative Infectious Diseases
OpenAlex ID: W4200628384