Distinct autoreactive CD19– plasma cell subsets accumulate in lupus-prone mice
- Van Duc Dang
- Franziska Szelinski
- Elodie Mohr
- Tuan Anh Le
- Jacob Ritter
- Annika Wiedemann
- Marta Ferreira-Gomes
- Gabriela Maria Guerra
- Pawel Durek
- Frederik Heinrich
- Hector Rincon-Arevalo
- Ana-Luisa Stefanski
- Eva Schrezenmeier
- Van T. Hoang
- Hong-Nhung Dao
- Soeren Ocvirk
- Qingyu Cheng
- Falk Hiepe
- Christian Hipfl
- Sebastian Hardt
- Max Löhning
- Liem Thanh Nguyen
- Mir-Farzin Mashreghi
- Simon Fillatreau
- Thomas Dörner
- Andreia C. Lino
2025-11-10
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 – PCs, particularly class-switched CXCR3⁺ and phosphatidylcholine-specific B-1–derived subsets, which exhibit unique gene expression profiles. We show that CD19 – PCs originate from CD19 + PCs in a unidirectional manner. Peripheral blood from SLE patients shows elevated frequencies of CD19 – PCs, implicating these cells in sustaining pathogenic activity. Our findings highlight the emergence of autoreactive CD19 – 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.