Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus

被引：14

作者：

Chen, Weirong ^{[1
]}

Hong, So-Hee ^{[1
,2
]}

Jenks, Scott A. ^{[1
]}

Anam, Fabliha A. ^{[1
]}

Tipton, Christopher M. ^{[1
]}

Woodruff, Matthew C. ^{[1
]}

Hom, Jennifer R. ^{[1
]}

Cashman, Kevin S. ^{[1
]}

Faliti, Caterina Elisa ^{[1
]}

Wang, Xiaoqian ^{[1
]}

Kyu, Shuya ^{[3
]}

Wei, Chungwen ^{[1
]}

Scharer, Christopher D. ^{[4
]}

Mi, Tian ^{[4
]}

Hicks, Sakeenah ^{[4
]}

Hartson, Louise ^{[1
]}

Nguyen, Doan C. ^{[3
]}

Khosroshahi, Arezou ^{[1
]}

Lee, Saeyun ^{[1
]}

Wang, Youliang ^{[1
]}

Bugrovsky, Regina ^{[1
]}

Ishii, Yusho ^{[1
]}

Lee, F. Eun-Hyung ^{[3
]}

Sanz, Ignacio ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Med, Div Rheumatol,Lowance Ctr Human Immunol, Atlanta, GA 30322 USA

[2] Ewha Womans Univ, Dept Microbiol, Seoul, South Korea

[3] Emory Univ, Sch Med, Div Pulm, Dept Med, Atlanta, GA 30322 USA

[4] Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA USA

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

基金：

美国国家卫生研究院;

关键词：

LYN TYROSINE KINASE; LIVED PLASMA-CELLS; BONE-MARROW; B-CELLS; DIFFERENTIATION; EXPRESSION; IL-10; IDENTIFICATION; ACTIVATION; GENERATION;

D O I：

10.1038/s41467-024-46053-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：17

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