title: TGF-β3 Inhibits Antibody Production by Human B Cells.
abstract: TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice. Murine CD4+CD25-LAG3+ regulatory T cells suppress B cell function through the production of TGF-β3, and it has been reported that TGF-β3 is therapeutic in a mouse model of systemic lupus erythematosus. The effect of TGF-β3 on human B cells has not been reported, and we herein examined the effect of TGF-β3 on human B cells. TGF-β3 suppressed B cell survival, proliferation, differentiation into plasmablasts, and antibody secretion. Although the suppression of human B cells by TGF-β1 has long been recognized, the precise mechanism for the suppression of B cell function by TGF-β1 remains elusive; therefore, we examined the effect of TGF-β1 and β3 on pathways important in B cell activation and differentiation. TGF-β1 and TGF-β3 inhibited some of the key molecules of the cell cycle, as well as transcription factors important in B cell differentiation into antibody secreting cells such as IRF4, Blimp-1, and XBP1. TGF-β1 and β3 also inhibited B cell receptor signaling. Our results suggest that TGF-β3 modifying therapy might be therapeutic in autoimmune diseases with B cell dysregulation in humans.
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Tsuchida
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Sumitomo
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ishigaki
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Laboratory for Autoimmune Diseases, Center for Integrative Medical Sciences, RIKEN, Yokohama, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kochi
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Tsuchiya
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mineto
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Komai
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Morita
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Max Planck-The University of Tokyo Center for Integrative Inflammology, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Keishi
authors.initials: K
authors.lastname: Fujio
mesh_terms: D000917:Antibody Formation / Q000187:drug effects*; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D000072377:Syk Kinase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012333:RNA, Messenger; D051785:Smad Proteins; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D053782:Transforming Growth Factor beta3; D000072377:Syk Kinase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase