title: Pre-existing CD19-independent GL7(-) Breg cells are expanded during inflammation and in mice with lupus-like disease.
abstract: Interleukin 10 (IL-10)-producing regulatory B-cells (Bregs) suppress inflammatory responses that mediate autoimmune diseases. However, it is unknown whether Bregs derive from a pre-existing dedicated B-cell lineage or if any B-cell can differentiate into Bregs in response to BCR or TLR activation. GL7(+) B-cells are antigen-experienced differentiated B-cells while GL7(-/lo) are at an early stage of B-cell differentiation. While both GL7(-/lo) and GL7(+) B cells can produce IL-10, differentiation of GL7(-) B-cells into Bregs does not require CD19- or Bcl6-induced signals, suggesting that BCR-induced proliferation or Ig class-switching is not necessary for generation of Breg cells. Of particular importance, we show that GL7(-) Breg cells are dramatically expanded in lupus-like mice and GL7(-) Bregs suppressed inflammatory responses in lupus-like mice by inducing expansion of Foxp3(+)Treg cells. Taken together, these results suggest that pre-existing GL7(-)IL-10(+) cells are expanded during inflammation, differentiate into GL7(+) Bregs and contribute to immune-regulation in lupus-like mice.
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: Xiaoqian
authors: X
authors: Wang
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310013, China.
authors: Yinxiang
authors: Y
authors: Wei
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: He
authors: H
authors: Xiao
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; Department of Nephrology, The 307th Hospital of Chinese People's Liberation Army, Beijing 100850, China.
authors: Xiaoling
authors: X
authors: Liu
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China; College of Pharmacy, Henan University, Kaifeng 475004, China.
authors: Yu
authors: Y
authors: Zhang
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: Gencheng
authors: G
authors: Han
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: Guojiang
authors: G
authors: Chen
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: Chunmei
authors: C
authors: Hou
authors: Department of Dermatology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing 100850, China.
authors: Li
authors: L
authors: Zhang
authors: Department of Rheumatology, First hospital of Jilin University, Changchun 130021, China.
authors: Ning
authors: N
authors: Ma
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: Beifen
authors: B
authors: Shen
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors: Yan
authors: Y
authors: Li
authors: Molecular Immunology Section, Laboratory of Immunology, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD 20892-1857, USA. Electronic address: egwuaguc@nei.nih.gov.
authors: Charles E
authors: CE
authors: Egwuagu
authors: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: wang_renxi@yahoo.com.
authors: Renxi
authors: R
authors: Wang
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr
chemical_list: D018941:Antigens, CD19; D000943:Antigens, Differentiation; C096712:antigen GL7
keywords: Bregs; CD19; GL7; Lupus; Tregs