Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19
Summary: In parasite and viral infections, aberrant B cell responses can suppress germinal center reactions thereby blunting long-lived memory and may provoke immunopathology including autoimmunity. Using COVID-19 as model, we set out to identify serological, cellular, and transcriptomic imprints of...
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2021
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oai:doaj.org-article:cae40debf2d347178638ee4c63b428502021-11-20T05:09:57ZMaturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-192589-004210.1016/j.isci.2021.103325https://doaj.org/article/cae40debf2d347178638ee4c63b428502021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221012943https://doaj.org/toc/2589-0042Summary: In parasite and viral infections, aberrant B cell responses can suppress germinal center reactions thereby blunting long-lived memory and may provoke immunopathology including autoimmunity. Using COVID-19 as model, we set out to identify serological, cellular, and transcriptomic imprints of pathological responses linked to autoreactive B cells at single-cell resolution. We show that excessive plasmablast expansions are prognostically adverse and correlate with autoantibody production but do not hinder the formation of neutralizing antibodies. Although plasmablasts followed interleukin-4 (IL-4) and BAFF-driven developmental trajectories, were polyclonal, and not enriched in autoreactive B cells, we identified two memory populations (CD80+/ISG15+ and CD11c+/SOX5+/T-bet+/−) with immunogenetic and transcriptional signs of autoreactivity that may be the cellular source of autoantibodies in COVID-19 and that may persist beyond recovery. Immunomodulatory interventions discouraging such adverse responses may be useful in selected patients to shift the balance from autoreactivity toward long-term memory.Christoph SchultheißLisa PascholdEdith WillscherDonjete SimnicaAnna WöstemeierFranziska MuscateMaxi WassStephan EisenmannJochen DutzmannGernot KeyßerNicola GaglianiMascha BinderElsevierarticleImmunologyVirologyTranscriptomicsScienceQENiScience, Vol 24, Iss 11, Pp 103325- (2021) |
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DOAJ |
| collection |
DOAJ |
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EN |
| topic |
Immunology Virology Transcriptomics Science Q |
| spellingShingle |
Immunology Virology Transcriptomics Science Q Christoph Schultheiß Lisa Paschold Edith Willscher Donjete Simnica Anna Wöstemeier Franziska Muscate Maxi Wass Stephan Eisenmann Jochen Dutzmann Gernot Keyßer Nicola Gagliani Mascha Binder Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19 |
| description |
Summary: In parasite and viral infections, aberrant B cell responses can suppress germinal center reactions thereby blunting long-lived memory and may provoke immunopathology including autoimmunity. Using COVID-19 as model, we set out to identify serological, cellular, and transcriptomic imprints of pathological responses linked to autoreactive B cells at single-cell resolution. We show that excessive plasmablast expansions are prognostically adverse and correlate with autoantibody production but do not hinder the formation of neutralizing antibodies. Although plasmablasts followed interleukin-4 (IL-4) and BAFF-driven developmental trajectories, were polyclonal, and not enriched in autoreactive B cells, we identified two memory populations (CD80+/ISG15+ and CD11c+/SOX5+/T-bet+/−) with immunogenetic and transcriptional signs of autoreactivity that may be the cellular source of autoantibodies in COVID-19 and that may persist beyond recovery. Immunomodulatory interventions discouraging such adverse responses may be useful in selected patients to shift the balance from autoreactivity toward long-term memory. |
| format |
article |
| author |
Christoph Schultheiß Lisa Paschold Edith Willscher Donjete Simnica Anna Wöstemeier Franziska Muscate Maxi Wass Stephan Eisenmann Jochen Dutzmann Gernot Keyßer Nicola Gagliani Mascha Binder |
| author_facet |
Christoph Schultheiß Lisa Paschold Edith Willscher Donjete Simnica Anna Wöstemeier Franziska Muscate Maxi Wass Stephan Eisenmann Jochen Dutzmann Gernot Keyßer Nicola Gagliani Mascha Binder |
| author_sort |
Christoph Schultheiß |
| title |
Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19 |
| title_short |
Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19 |
| title_full |
Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19 |
| title_fullStr |
Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19 |
| title_full_unstemmed |
Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19 |
| title_sort |
maturation trajectories and transcriptional landscape of plasmablasts and autoreactive b cells in covid-19 |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/cae40debf2d347178638ee4c63b42850 |
| work_keys_str_mv |
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| _version_ |
1718419567840067584 |