A distinct effector B cell population drives autoantibody production in SARS-CoV-2 infection.

Double-negative 2 (DN2) atypical memory B cells are identified as key precursors of autoantibody-producing cells during SARS-CoV-2 infection, especially in autoAb-high individuals.

• Why it matters: Understanding the cellular origins of autoantibodies in COVID-19 is crucial because they are linked to mortality and Long COVID, yet their source remains unclear, hindering targeted interventions.
• What they did: The study analyzed 12 matched participants using single-cell RNA-seq, ATAC-seq, proteomics, autoAb profiling, and in vitro assays, revealing that autoAb abundance correlates with AtMs contraction and is associated with DN2s exhibiting increased TLR7 signaling and autoimmune trait heritability.
• The result: Findings suggest DN2s are central to autoAb production in SARS-CoV-2 infection, providing insights into autoimmune responses and potential targets for therapeutic strategies.