Distinct autoreactive CD19– plasma cell subsets accumulate in lupus-prone mice
Plasma cells (PC) participate in the pathogenesis of systemic lupus erythematosus (SLE) through sustained autoantibody and inflammatory cytokine secretion. Current PC-depleting therapies risk eliminating protective long-lived PCs, highlighting the need to identify pathogenic subsets for selective targeting. Here, using single-cell RNA sequencing, B cell receptor repertoire analysis, and genetic models, we identify disease- and organ-specific PCs in lupus-prone mice. We find a substantial expansion of autoreactive CD19<sup>-</sup> PCs, particularly class-switched CXCR3⁺ and phosphatidylcholine-specific B-1-derived subsets, which exhibit unique gene expression profiles. We show that CD19<sup>-</sup> PCs originate from CD19<sup>+</sup> PCs in a unidirectional manner. Peripheral blood from SLE patients shows elevated frequencies of CD19<sup>-</sup> PCs, implicating these cells in sustaining pathogenic activity. Our findings highlight the emergence of autoreactive CD19<sup>-</sup> PCs as a critical feature of lupus pathogenesis in mice and underscore the need for therapeutic approaches that extend beyond CD19-targeting to improve treatment strategies in SLE.
Authors
- Van Duc Dang (ORCID: https://orcid.org/0000-0002-0403-6479)
- Ana‐Luisa Stefanski (ORCID: https://orcid.org/0000-0001-7689-6454)
- Jacob Ritter (ORCID: https://orcid.org/0000-0001-8962-1564)
- Max Löhning (ORCID: https://orcid.org/0000-0001-6382-7281)
- Sebastian Hardt (ORCID: https://orcid.org/0000-0001-8774-7585)
- Van T. Hoang (ORCID: https://orcid.org/0000-0002-9613-6572)
- Falk Hiepe (ORCID: https://orcid.org/0000-0003-3584-5292)
- Annika Wiedemann (ORCID: https://orcid.org/0000-0002-0013-6579)
- Simon Fillatreau (ORCID: https://orcid.org/0000-0002-7730-9917)
- Eva Vanessa Schrezenmeier (ORCID: https://orcid.org/0000-0002-0016-7885)
- Pawel Durek (ORCID: https://orcid.org/0000-0002-6179-0670)
- Mir‐Farzin Mashreghi (ORCID: https://orcid.org/0000-0002-8015-6907)
- Héctor Rincón-Arévalo (ORCID: https://orcid.org/0000-0001-5614-7894)
- Franziska Szelinski (ORCID: https://orcid.org/0000-0001-7850-5971)
- Andreia C. Lino (ORCID: https://orcid.org/0000-0002-3791-8232)
- Elodie Mohr (ORCID: https://orcid.org/0000-0003-3406-7302)
- Christian Hipfl (ORCID: https://orcid.org/0000-0003-2538-7566)
- Tuan Anh Le (ORCID: https://orcid.org/0000-0003-3239-7287)
- Frederik Heinrich (ORCID: https://orcid.org/0000-0001-6097-5422)
- Soeren Ocvirk (ORCID: https://orcid.org/0000-0001-6547-2445)
- Gabriela Maria Guerra (ORCID: https://orcid.org/0000-0002-9773-4929)
- Marta Ferreira‐Gomes (ORCID: https://orcid.org/0000-0002-7171-7952)
- Thomas Dörner (ORCID: https://orcid.org/0000-0002-6478-7725)
- Nguyễn Thanh Liêm (ORCID: https://orcid.org/0000-0002-4036-0161)
- Qingyu Cheng
- H. Dao
Institutions
- Hôpital Necker-Enfants Malades (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Vietnam National University, Hanoi (VN)
- Université Paris Cité (FR)
- Universidad de Antioquia (CO)
- Humboldt-Universität zu Berlin (DE)
- Institut Necker Enfants Malades (FR)
- German Rheumatism Research Centre (DE)
- Assistance Publique – Hôpitaux de Paris (FR)
- Vinmec Times City International Hospital (VN)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- VinUniversity (VN)
- German Institute of Human Nutrition (DE)
- VNU University of Science (VN)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-10
- DOI
- https://doi.org/10.1038/s41467-025-65906-6
- Primary Topic
- Systemic Lupus Erythematosus Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS)
- Tập đoàn Vingroup - Công ty CP
- Deutsche Forschungsgemeinschaft