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

• DOI: 10.1016/j.isci.2021.103325
• Publication Date: 2021-10-25T21:22:26Z
• Authors: Christoph Schultheiß; Lisa Paschold; Edith Willscher; Donjete Simnica; Anna Wöstemeier; Franziska Muscate; Maxi Wass; Stephan Eisenmann; Jochen Dutzmann; Gernot Keyßer; Nicola Gagliani; Mascha Binder
• Keywords: 03 medical and health sciences; 0302 clinical medicine; Virology; Science; Immunology; Q; Transcriptomics; Article; 3. Good health

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.