Distinct autoreactive CD19– plasma cell subsets accumulate in lupus-prone mice

This is the authors' abstract. We don't add key points for this paper.

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.