期刊
NATURE IMMUNOLOGY
卷 21, 期 12, 页码 1506-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-020-00814-z
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资金
- National Institutes of Health grants [UL TR000424, R01-AG054991, U19-AI110483, P01-AI125180-01, R37-AI049660, 1R01AI121252, 1U01AI141993, R01 AI127828, T32-HL116271-07]
- HHS/NIAID/NIH contract [75N93019C00074]
- Defense Advanced Research Project Agency [HR001117S0019]
- Dolly Parton COVID-19 Research Fund at Vanderbilt
- Fast Grants Award
A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings. Extrafollicular activation correlated strongly with large antibody-secreting cell expansion and early production of high concentrations of SARS-CoV-2-specific neutralizing antibodies. Yet, these patients had severe disease with elevated inflammatory biomarkers, multiorgan failure and death. Overall, these findings strongly suggest a pathogenic role for immune activation in subsets of patients with COVID-19. Our study provides further evidence that targeted immunomodulatory therapy may be beneficial in specific patient subpopulations and can be informed by careful immune profiling. Sanz and colleagues examine B cell subsets in a cohort of patients with COVID-19. Severely ill patients have higher frequencies of activated extrafollicular T-bet(+)B cells that form antibody-secreting cells, the majority of which express germline sequences and are reminiscent of antibody responses observed in patients with systemic lupus erythematosus during flares.
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