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. Graphical abstract Highlights • 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 populations Immunology; Virology; Transcriptomics
【저자키워드】 immunology, Virology, transcriptomics, 【초록키워드】 COVID-19, Autoimmunity, Neutralizing antibodies, disease severity, B cells, Intervention, immunopathology, viral infections, Population, memory, B cell, response, Patient, serological, single-cell, BCR, IL-4, cellular, Atypical, autoantibody, B cell response, Trajectories, Abstract, reaction, plasmablast, pathological response, CD80, CD11c, transcriptomic, polyclonal, transcriptional, blunting, selected, identify, suppress, developmental, IGHV4-34, provoke, 【제목키워드】 COVID-19, B cell, trajectory, plasmablast, transcriptional,