ImmunityAug 28, 2026

A specific type of antibody-producing B cell linked to autoantibodies in COVID-19 infection

Updated Aug 29, 2026

Abstract

Analysis of 12 participants revealed that autoantibody abundance inversely correlated with neutralizing IgG levels during SARS-CoV-2 infection.

As SARS-CoV-2 infection resolved, autoantibody levels decreased alongside a reduction in atypical memory B cells.
In vitro experiments indicated that atypical memory B cells preferentially transformed into antibody-secreting cells when stimulated.
Individuals with high autoantibody levels exhibited heightened TLR7 signaling and oxidative stress in specific atypical memory B cells.
Atypical memory B cells in autoantibody-rich individuals showed regulatory changes influenced by specific transcription factors.
Genetic analysis suggested a strong link between certain B cell subsets and the heritability of autoimmune traits.

Simplified

Autoantibodies (autoAbs) are linked to mortality and Long COVID, yet their cellular origins remain unclear. We analyzed the INCOV cohort and identified 12 age- and sex-matched participants with varying autoAb abundance and integrated single-cell RNA-seq and ATAC-seq data from B cells, plasma proteomics, proteome-wide autoAb profiling, clinical data, and in vitro assays. AutoAb abundance inversely correlated with neutralizing IgG and declined as infection resolved, paralleling the contraction of atypical memory B cells (AtMs). In vitro, AtMs preferentially differentiated into autoAb-producing antibody-secreting cells upon TLR7/8 stimulation. CD11c⁺ AtMs (double-negative 2, DN2s) in autoAb-high individuals exhibited increased TLR7 signaling, oxidative stress, and isotype switching, regulated by transcription factors T-bet and XBP1. Integrated genetic and genomic analyses showed that DN2s had the strongest enrichment for autoimmune trait heritability and inferred regulatory effects of autoimmune risk variants among B cell subsets. These findings identify DN2s as key precursors of autoAb-producing cells during SARS-CoV-2 infection.

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A specific type of antibody-producing B cell linked to autoantibodies in COVID-19 infection

Abstract

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