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 and correlate with autcantibody production but do not hinder the formation of neutralizing antibc dies. 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.

Automated summary

In the context of parasite and viral infections, aberrant B cell responses can lead to immunopathology including autoimmunity. Using COVID-19 as a model, researchers identified excessive plasmablast expansions associated with autoantibody production, while also pinpointing two memory cell populations as potential sources of autoantibodies in the disease. Efforts to discourage adverse immune responses may help shift the balance from autoreactivity towards long-term memory in selected patients.