Work

Heterogeneity of in vitro generated primary human antibody secreting cells of Systemic Lupus Erythematosus (SLE) patients 2667

Year: 2025

Type: article

Abstract: Description SLE is an autoimmune disease characterized by pathogenic autoantibodies (autoAbs) produced by terminally differentiated B lineage antibody-secreting cells (ASCs). The expanded double negative 2 (DN2) B cell subset found in SLE patients gives rise to autoAb-producing ASCs. While many B cell subsets can form ASCs, it’s unclear whether ASCs derived from specific B cell populations, isolated from either SLE or healthy donors (HD), exhibit distinct functional or pathogenic attributes. Using our novel two-step culture system, we generated ASCs in vitro from resting naïve (rNav-ASCs), resting switched memory (rSW-ASCs), and DN2 (DN2-ASCs) primary human B cell subsets isolated from HDs and SLE patients (n = 3-5). Bulk RNA-sequencing revealed differentially expressed genes and enriched pathways between ASCs generated from different B cell subsets. Notably, CXCR3, which directs cells to inflamed tissues, was upregulated in SLE-derived DN2-ASCs relative to rSW-ASCs. Moreover, we identified differences between ASCs generated from phenotypically matched subsets isolated from SLE and HD, with enrichment for inflammatory signatures within SLE rSW-ASCs. Thus, while DN2 cells are thought to be major contributors to SLE pathogenesis, the gene signature of SLE rSW-ASCs suggest rSW memory B cells may also contribute to pathogenesis. We are now performing functional assays to identify key regulators controlling the distinct attributes of ASCs derived from different B subsets in SLE patients. Funding Sources Funding from P01 AI125180 and the Lupus Research Alliance Topic Categories Basic Autoimmunity (BA)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.558