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- Title
Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus.
- Authors
Weirong Chen; So-Hee Hong; Jenks, Scott A.; Anam, Fabliha A.; Tipton, Christopher M.; Woodruff, Matthew C.; Hom, Jennifer R.; Cashman, Kevin S.; Faliti, Caterina Elisa; Xiaoqian Wang; Kyu, Shuya; Chungwen Wei; Scharer, Christopher D.; Mi, Tian; Hicks, Sakeenah; Hartson, Louise; Nguyen, Doan C.; Khosroshahi, Arezou; Lee, Saeyun; Wang, Youliang
- Abstract
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19-CD138+ ASC, similar to bone marrow LLPC. ASC from patients with SLE displayed morphological features of premature maturation and a transcriptome epigenetically initiated in SLE B cells. ASC from patients with SLE exhibited elevated protein levels of CXCR4, CXCR3 and CD138, along with molecular programs that promote survival. Furthermore, they demonstrate autocrine production of APRIL and IL-10, which contributed to their prolonged in vitro survival. Our work provides insight into the mechanisms of generation, expansion, maturation and survival of SLE ASC.
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-46053-w