Maturation Trajectories and Transcriptional Landscape of Plasmablasts and Autoreactive B Cells in COVID-19

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, correlate with auto-antibody production, but do not hinder the formation of neutralizing antibodies. While plasmablasts followed 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 auto-antibodies 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 towards long-term memory. Funding Information: This project was partially funded by the CRC 841 of the German Research Foundation (to MB) as well as by the Martin-Luther-University Halle (Saale). Declaration of Interests: The authors declare no competing interests.