TY - JOUR
T1 - Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus
AU - Chen, Weirong
AU - Hong, So Hee
AU - Jenks, Scott A.
AU - Anam, Fabliha A.
AU - Tipton, Christopher M.
AU - Woodruff, Matthew C.
AU - Hom, Jennifer R.
AU - Cashman, Kevin S.
AU - Faliti, Caterina Elisa
AU - Wang, Xiaoqian
AU - Kyu, Shuya
AU - Wei, Chungwen
AU - Scharer, Christopher D.
AU - Mi, Tian
AU - Hicks, Sakeenah
AU - Hartson, Louise
AU - Nguyen, Doan C.
AU - Khosroshahi, Arezou
AU - Lee, Saeyun
AU - Wang, Youliang
AU - Bugrovsky, Regina
AU - Ishii, Yusho
AU - Lee, F. Eun Hyung
AU - Sanz, Ignacio
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85186588608&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-46053-w
DO - 10.1038/s41467-024-46053-w
M3 - Article
C2 - 38429276
AN - SCOPUS:85186588608
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1899
ER -
