title: BIP induces mice CD19(hi) regulatory B cells producing IL-10 and highly expressing PD-L1, FasL.
abstract: Many studies have shown that B cells possess a regulatory function in mouse models of autoimmune diseases. Regulatory B cells can modulate immune response through many types of molecular mechanisms, including the production of IL-10 and the expression of PD-1 Ligand and Fas Ligand, but the microenvironmental factors and mechanisms that induce regulatory B cells have not been fully identified. BIP (binding immunoglobulin protein), a member of the heat shock protein 70 family, is a type of evolutionarily highly conserved protein. In this article, we have found that IL-10(+), PD-L1(hi) and FasL(hi) B cells are discrete cell populations, but enriched in CD19(hi) cells. BIP can induce IL-10-producing splenic B cells, IL-10 secretion and B cells highly expressing PD-L1 and FasL. CD40 signaling acts in synergy with BIP to induce regulatory B cells. BIP increased surface CD19 molecule expression intensity and IL-10(+), PD-L1(hi) and FasL(hi) B cells induced by BIP share the CD19(hi) phenotype. Furthermore, B cells treated with BIP and anti-CD40 can lead to suppression of T cell proliferation and the effect is partially IL-10-dependent and mainly BIP-induced. Taken together, our findings identify a novel function of BIP in the induction of regulatory B cells and add a new reason for the therapy of autoimmune disorders or other inflammatory conditions.
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Youfa
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yanghui
authors.initials: Y
authors.lastname: Ou
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qing
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Wuhan General Hospital of Guangzhou Command, Wuhan 430070, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Huifen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Feili
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: myjsz@mails.tjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.affiliation: Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D060890:B7-H1 Antigen / Q000096:biosynthesis / Q000276:immunology; D000091342:Endoplasmic Reticulum Chaperone BiP; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006360:Heat-Shock Proteins / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D018941:Antigens, CD19; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006360:Heat-Shock Proteins; C556062:IL10 protein, mouse; D016753:Interleukin-10
keywords: BIP; FasL; IL-10; PD-L1; Regulatory B cells