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

Medientyp: E-Artikel

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

Beteiligte: Schultheiß, Christoph [VerfasserIn]; Paschold, Lisa [VerfasserIn]; Willscher, Edith [VerfasserIn]; Simnica, Donjete [VerfasserIn]; Wöstemeier, Anna [VerfasserIn]; Muscate, Franziska [VerfasserIn]; Wass, Maxi [VerfasserIn]; Eisenmann, Stephan [VerfasserIn]; Dutzmann, Jochen [VerfasserIn]; Keyßer, Gernot [VerfasserIn]; Gagliani, Nicola [VerfasserIn]; Binder, Mascha [VerfasserIn]

Erschienen: 2021

Sprache: Englisch

DOI: 10.1016/j.isci.2021.103325

ISSN: 2589-0042

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Beschreibung: 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.

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Rechte-/Nutzungshinweise: Namensnennung (CC BY)

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