期刊
SCIENCE IMMUNOLOGY
卷 7, 期 68, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciimmunol.abl5652
关键词
-
类别
资金
- National Institutes of Health [T32GM136651, F30HL149151, F30CA250249, F30CA239444, T32AI007019, T32AI007517, R37AR040072, R01AR074545, K08AI128043, R01AI148467, R01AI136942]
- Graduate School of Arts and Sciences
- Gershon-Trudeau Fellowship from the Department of Immunobiology of Yale University
- Bill & Melinda Gates Foundation
- DoD grant [IIAR W81XWH-21-1-0019]
- Burroughs Wellcome Fund Career Award for Medical Scientists
- Mathers Charitable Foundation
- Ludwig Family Foundation
- Emergent Ventures Fast Grants
This study found that both T-FH-dependent and -independent antibodies were induced against SARS-CoV-2 infection, vaccination, and influenza A virus infection. The T-FH-independent antibodies had reduced somatic hypermutation but were still high affinity and capable of neutralizing diverse spike-derived epitopes and variants of concern.
T follicular helper (T-FH) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of T-FH 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, noncanonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both T-FH-dependent and -independent antibodies were induced against SARS-CoV-2 infection, SARS-CoV-2 vaccination, and influenza A virus infection. Although T-FH-independent antibodies to SARS-CoV-2 had evidence of reduced somatic hypermutation, they were still high affinity, durable, and reactive against diverse spike-derived epitopes and were capable of neutralizing both homologous SARS-CoV-2 and the B.1.351 (beta) variant of concern. We found by epitope mapping and B cell receptor sequencing that T-FH cells focused the B cell response, and therefore, in the absence of T-FH cells, a more diverse clonal repertoire was maintained. These data support an alternative pathway for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GC-derived antibodies that might compensate for GCs damaged by viral inflammation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据