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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221012943 |
| _version_ | 1818743379697074176 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T02:27:29Z |
| format | Article |
| id | doaj.art-cae40debf2d347178638ee4c63b42850 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-18T02:27:29Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-cae40debf2d347178638ee4c63b428502022-12-21T21:24:00ZengElsevieriScience2589-00422021-11-012411103325Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19Christoph Schultheiß0Lisa Paschold1Edith Willscher2Donjete Simnica3Anna Wöstemeier4Franziska Muscate5Maxi Wass6Stephan Eisenmann7Jochen Dutzmann8Gernot Keyßer9Nicola Gagliani10Mascha Binder11Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), GermanyDepartment of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), GermanyDepartment of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), GermanyDepartment of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), GermanyI. Department of Medicine and Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyI. Department of Medicine and Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, GermanyDepartment of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), GermanyDepartment of Internal Medicine I, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanyMid-German Heart Center, Department of Cardiology and Intensive Care Medicine, University Hospital, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), GermanyDepartment of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanyI. Department of Medicine and Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institute and University Hospital, Stockholm, SwedenDepartment of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), Germany; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004221012943ImmunologyVirologyTranscriptomics |
| spellingShingle | 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 iScience Immunology Virology Transcriptomics |
| title | 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_short | 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 |
| topic | Immunology Virology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221012943 |
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