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

共 88 条

[61] Neutrophil-Mediated IFN Activation in the Bone Marrow Alters B Cell Development in Human and Murine Systemic Lupus Erythematosus [J].

Palanichamy, Arumugam ;

Bauer, Jason W. ;

Yalavarthi, Srilakshmi ;

Meednu, Nida ;

Barnard, Jennifer ;

Owen, Teresa ;

Cistrone, Christopher ;

Bird, Anna ;

Rabinovich, Alfred ;

Nevarez, Sarah ;

Knight, Jason S. ;

Dedrick, Russell ;

Rosenberg, Alexander ;

Wei, Chungwen ;

Rangel-Moreno, Javier ;

Liesveld, Jane ;

Sanz, Inaki ;

Baechler, Emily ;

Kaplan, Mariana J. ;

Anolik, Jennifer H. .

JOURNAL OF IMMUNOLOGY, 2014, 192 (03) :906-918

[62] Increased Toll-Like Receptors Activity and TLR Ligands in Patients with Autoimmune Thyroid Diseases [J].

Peng, Shiqiao ;

Li, Chenyan ;

Wang, Xinyi ;

Liu, Xin ;

Han, Cheng ;

Jin, Ting ;

Liu, Shanshan ;

Zhang, Xiaowen ;

Zhang, Hanyi ;

He, Xue ;

Xie, Xiaochen ;

Yu, Xiaohui ;

Wang, Chuyuan ;

Shan, Ling ;

Fan, Chenling ;

Shan, Zhongyan ;

Teng, Weiping .

FRONTIERS IN IMMUNOLOGY, 2016, 7

[63] Mcl-1 is essential for the survival of plasma cells [J].

Peperzak, Victor ;

Vikstroem, Ingela ;

Walker, Jennifer ;

Glaser, Stefan P. ;

LePage, Melanie ;

Coquery, Christine M. ;

Erickson, Loren D. ;

Fairfax, Kirsten ;

Mackay, Fabienne ;

Strasser, Andreas ;

Nutt, Stephen L. ;

Tarlinton, David M. .

NATURE IMMUNOLOGY, 2013, 14 (03) :290-297

[64] Progressive Upregulation of Oxidative Metabolism Facilitates Plasmablast Differentiation to a T-Independent Antigen [J].

Price, Madeline J. ;

Patterson, Dillon G. ;

Scharer, Christopher D. ;

Boss, Jeremy M. .

CELL REPORTS, 2018, 23 (11) :3152-3159

[65] Elucidation of Seventeen Human Peripheral Blood B-Cell Subsets and Quantification of the Tetanus Response Using a Density-Based Method for the Automated Identification of Cell Populations in Multidimensional Flow Cytometry Data [J].

Qian, Yu ;

Wei, Chungwen ;

Lee, F. Eun-Hyung ;

Campbell, John ;

Halliley, Jessica ;

Lee, Jamie A. ;

Cai, Jennifer ;

Kong, Y. Megan ;

Sadat, Eva ;

Thomson, Elizabeth ;

Dunn, Patrick ;

Seegmiller, Adam C. ;

Karandikar, Nitin J. ;

Tipton, Christopher M. ;

Mosmann, Tim ;

Sanz, Inaki ;

Scheuermann, Richard H. .

CYTOMETRY PART B-CLINICAL CYTOMETRY, 2010, 78B :S69-S82

[66] Transcriptional and Metabolic Control of Memory B Cells and Plasma Cells [J].

Ripperger, Tyler J. ;

Bhattacharya, Deepta .

ANNUAL REVIEW OF IMMUNOLOGY, VOL 39, 2021, 39 :345-368

[67] Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan [J].

Robinson, Marcus James ;

Ding, Zhoujie ;

Dowling, Mark R. ;

Hill, Danika L. ;

Webster, Rosela H. ;

McKenzie, Craig ;

Pitt, Catherine ;

O'Donnell, Kristy ;

Mulder, Jesse ;

Brodie, Erica ;

Hodgkin, Philip D. ;

Wong, Nick C. ;

Quast, Isaak ;

Tarlinton, David M. .

IMMUNITY, 2023, 56 (07) :1596-+

[68] LONG-TERM CULTURED CD40-ACTIVATED B-LYMPHOCYTES DIFFERENTIATE INTO PLASMA-CELLS IN RESPONSE TO IL-10 BUT NOT IL-4 [J].

ROUSSET, F ;

PEYROL, S ;

GARCIA, E ;

VEZZIO, N ;

ANDUJAR, M ;

GRIMAUD, JA ;

BANCHEREAU, J .

INTERNATIONAL IMMUNOLOGY, 1995, 7 (08) :1243-1253

[69] Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1 [J].

Saveliev, Alexander ;

Bell, Sarah E. ;

Turner, Martin .

JOURNAL OF EXPERIMENTAL MEDICINE, 2021, 218 (03)

[70] Epigenetic programming underpins B cell dysfunction in human SLE [J].

Scharer, Christopher D. ;

Blalock, Emily L. ;

Mi, Tian ;

Barwick, Benjamin G. ;

Jenks, Scott A. ;

Deguchi, Tsuneo ;

Cashman, Kevin S. ;

Neary, Bridget E. ;

Patterson, Dillon G. ;

Hicks, Sakeenah L. ;

Khosroshahi, Arezou ;

Lee, F. Eun-Hyung ;

Wei, Chungwen ;

Sanz, Inaki ;

Boss, Jeremy M. .

NATURE IMMUNOLOGY, 2019, 20 (08) :1071-+

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