title: Combination of TACI-IgG and anti-IL-15 treats murine lupus by reducing mature and memory B cells.
abstract: Clinical trials suggest that BAFF inhibitors such as atacicept (TACI-IgG) and belimumab (anti-BAFF antibody) could not reduce memory B-cell numbers, although they reduced the numbers of CD20(+) naïve B cells and activated B cells. In the present study, we explored the way to reduce memory B-cell numbers. First, we used TACI-IgG to treat murine lupus. We found that TACI-IgG was effective in reducing mature B cell numbers. Accordingly it controlled the level of the anti-dsDNA antibody in lupus-like mice. In addition, TACI-IgG up-regulated memory B cells in murine lupus. Furthermore, we found that TACI-IgG up-regulated IL-15 expression in lupus-like mice. Thus, the combination of TACI-IgG and anti-IL-15 antibodies was explored to understand their effects on the treatment of murine lupus. Compared to treatments with TACI-IgG or anti-IL-15 alone, the combination of TACI-IgG and anti-IL-15 antibodies efficiently ameliorated murine lupus phenotypes. The study provides hints for the clinical application of BAFF- and IL-15-specific therapeutic agents.
authors.affiliation: Department of Rheumatology, First Hospital of Jilin University, Changchun 130021, China; Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: He
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1857, USA.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Marrero
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xing
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Immunology, Medical College of Henan University, Kaifeng 475001, China.
authors.forename: Mingke
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Gencheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Guojiang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Hou
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Renxi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Rheumatology, First Hospital of Jilin University, Changchun 130021, China. Electronic address: jlujzy@yahoo.com.cn.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D053264:B-Cell Activating Factor / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology; D004359:Drug Therapy, Combination; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D019409:Interleukin-15 / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000628:therapy*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D061067:Antibodies, Monoclonal, Humanized; D053264:B-Cell Activating Factor; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D011993:Recombinant Fusion Proteins; C511911:belimumab; D004247:DNA; C524618:TACI receptor-IgG Fc fragment fusion protein
keywords: IL-15; Lupus; Memory B cells; TACI-IgG