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

Eduard Nitschke; Van Duc Dang; Hector Rincon-Arevalo; Franziska Szelinski; Jacob Ritter; Eva Schrezenmeier; Tobias Alexander; Tuan Anh Le; Yidan Chen; Annika Wiedemann; Jose-Bernardino Gonzalez; Andreia C Lino; Ana-Luisa Stefanski; Thomas Dörner

doi:10.3389/fimmu.2025.1585953

Phosphatidylcholine-specific B cells are enriched among atypical CD11c^high and CD21^low memory B cells in antiphospholipid syndrome

Front Immunol. 2025 Jun 3:16:1585953. doi: 10.3389/fimmu.2025.1585953. eCollection 2025.

Authors

Eduard Nitschke^{1

2}, Van Duc Dang^{1

2

3}, Hector Rincon-Arevalo^{1

2

4

5}, Franziska Szelinski^{1

2}, Jacob Ritter^{1

2}, Eva Schrezenmeier^{1

2

5

6}, Tobias Alexander^{1

2}, Tuan Anh Le^{1

2}, Yidan Chen^{1

2}, Annika Wiedemann^{1

2}, Jose-Bernardino Gonzalez^{7

8}, Andreia C Lino², Ana-Luisa Stefanski^{1

2}, Thomas Dörner^{1

2}

Affiliations

¹ Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
² German Rheumatism Research Centre, German Rheumatism Research Centre, Berlin, Germany.
³ Faculty of Biology, VNU University of Science, Vietnam National University, Hanoi, Vietnam.
⁴ Grupo de Inmunologiía Celular e Inmunogeneítica, Facultad de Medicina, Universidad de Antioquia UdeA, Instituto de Investigaciones Meídicas, Medelliín, Colombia.
⁵ Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁶ Berlin Institute of Health | Chariteí - Universitaütsmedizin Berlin, BIH Academy, Berlin, Germany.
⁷ Clinical Chemistry and Pathobiochemistry, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute for Laboratory Medicine, Berlin, Germany.
⁸ Laboratoriumsmedizin & Toxikologie, Labor Berlin-Charité Vivantes GmbH, Berlin, Germany.

Abstract

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^lowCD11c^high unswitched and switched memory B cells in both pAPS and sAPS.

Conclusion: The enrichment of PtC-specific B cells among CD21^low and CD11c^high atypical memory subsets, along with their correlation with aPL serum levels, suggest a linkage between these atypical memory B cell subsets and autoantibody producing cells in APS.

Keywords: APS - antiphospholipid syndrome; B cells; adaptive immunity; anti-phospholipid antibodies; antigen-specific B cells; primary APS; secondary APS.

MeSH terms

Adult
Antibodies, Antiphospholipid / blood
Antibodies, Antiphospholipid / immunology
Antiphospholipid Syndrome* / immunology
B-Lymphocyte Subsets* / immunology
B-Lymphocyte Subsets* / metabolism
B-Lymphocytes / immunology
Case-Control Studies
Female
Flow Cytometry
Humans
Immunologic Memory
Male
Memory B Cells* / immunology
Memory B Cells* / metabolism
Middle Aged
Phosphatidylcholines* / immunology
Receptors, Complement 3d / metabolism

Substances

Antibodies, Antiphospholipid
Phosphatidylcholines
Receptors, Complement 3d