Phosphatidylcholine-specific B cells are enriched among atypical CD11chigh and CD21low memory B cells in antiphospholipid syndrome

作者：Eduard Nitschke, Van Duc Dang, Héctor Rincón-Arévalo, Franziska Szelinski, Jacob Ritter, Eva Schrezenmeier, Tobias Alexander, Tuấn Anh Lê, Yidan Chen, Annika Wiedemann, Jeffrey S. Gonzalez, Andreia C. Lino, Ana‐Luisa Stefanski, Thomas E. Dorner · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1585953 · 被引用次数：2 · 研究领域：Systemic Lupus Erythematosus Research、Platelet Disorders and Treatments、Liver Diseases and Immunity

Background Patients with antiphospholipid syndrome (APS) carry an increased risk of thrombosis and adverse pregnancy outcomes due to the presence of antiphospholipid autoantibodies (aPL). However, the pathogenesis of the disease remains incompletely understood regarding various aPL and the role of autoreactive B cells as precursors of antibody-secreting plasma cells (PC). Objective To assess B-cell dysregulation in APS, with a focus on the distribution of B cell subsets and phosphatidylcholine (PtC)-specific cells. Methods We used flow cytometry to study B cell subsets in peripheral blood mononuclear cells (PBMCs) from 20 healthy controls (HCs), 21 patients with primary APS (pAPS), and 16 patients with secondary APS (sAPS). A novel fluorescent liposome-based method was used to identify PtC-specific B cells in these subsets. Data were analyzed using manual gating and unsupervised clustering. We quantified aPtC antibody serum levels using ELISA and conducted correlation analyses between PtC-specific B cell subsets and aPL titers. Results Patients with pAPS and sAPS exhibited significantly increased frequencies of atypical CD21 low and CD11c high B cells, including PtC-specific B cells. Notably, both total and unswitched memory PtC-specific B cells were elevated in pAPS patients and correlated with aPL antibody titers. Unsupervised clustering further highlighted the increased frequencies of PtC-specific CD21 low CD11c high unswitched and switched memory B cells in both pAPS and ...