摘要：SummaryIn 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.Graphical abstractDisplay OmittedHighlights•Plasmablast expansions correlate with disease severity and autoantibodies in COVID-19•Patients with high plasmablast levels exhibit IGHV4-34 skewing•Autoreactive BCRs are enriched in atypical memory, not plasmablast populationsImmunology; Virology; Transcriptomics
