Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22210-3
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Funding
- state of Berlin
- European Regional Development Fund [EFRE 1.8/11]
- Berlin Institute of Health
- Deutsche Forschungsgemeinschaft (DFG) [TRR130-P16, TRR241-B03, TRR130-P17]
- European Research Council through the Advanced Grant IMMEMO [ERC-2010-AdG.20100317, 268978]
- Leibniz Association (Leibniz Collaborative Excellence) [CHROQ K121-2018]
- DFG [TRR130-P17, TRR241-A04, TRR130-C01, HA5354/6-2, HA5354/8-2, 389687267]
- Russian Ministry of Science and Higher Education of the Russian Federation [075-15-2019-1660]
- Russian foundation for basic research [17-00-00435]
- Dr. Rolf M. Schwiete Foundation
- Deutsche Forschungsgemeinschaft [324392634-TRR221]
- German Federal Ministry of Education and Research (BMBF) [COVID19-014 01KI2043A CoVER-Ab]
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The study found that in severe COVID-19 patients, plasmablasts shift from IFN to TGF-beta instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.
The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-beta, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-beta. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-beta, and is distracted from itself. Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGF beta instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.
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