Maturation trajectories and transcriptional landscape of plasmablasts and autoreactive B cells in COVID-19

iScience

Mascha Binder¹  Stephan Eisenmann²  Gernot Keyßer³  Christoph Schultheiß⁴  Donjete Simnica⁴  Edith Willscher⁴  Lisa Paschold⁴  Maxi Wass⁴  Nicola Gagliani⁵  Anna Wöstemeier⁵  Franziska Muscate⁵  Jochen Dutzmann⁶ 

[1] Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Department of Internal Medicine I, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany;Department of Internal Medicine II, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany;Department of Internal Medicine IV, Oncology/Hematology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, 06120 Halle (Saale), Germany;I. Department of Medicine and Department for General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Mid-German Heart Center, Department of Cardiology and Intensive Care Medicine, University Hospital, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany;

关键词: Immunology;    Virology;    Transcriptomics;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown