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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月10日

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  • 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

摘要

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.