Combination of TACI-IgG and anti-IL-15 treats murine lupus by reducing mature and memory B cells

• Published in: Cellular immunology Vol. 289; no. 1-2; pp. 140 - 144
• Main Authors: Ma, Ning, Xiao, He, Marrero, Bernadette, Xing, Chen, Wang, Xiaoqian, Zheng, Mingke, Han, Gencheng, Chen, Guojiang, Hou, Chunmei, Shen, Beifen, Li, Yan, Wang, Renxi, Jiang, Zhenyu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2014
• Subjects: Animals; Antibodies, Antinuclear - immunology; Antibodies, Monoclonal, Humanized - therapeutic use; B-Cell Activating Factor - immunology; B-Lymphocytes - immunology; DNA - immunology; Drug Therapy, Combination; IL-15; Immunologic Memory - drug effects; Immunologic Memory - immunology; Immunosuppressive Agents - therapeutic use; Interleukin-15 - immunology; Lupus; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - therapy; Lymphocyte Activation - immunology; Lymphocyte Count; Memory B cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred NZB; Recombinant Fusion Proteins - therapeutic use; Signal Transduction - immunology; TACI-IgG; Lupus; TACI-IgG; IL-15; Memory B cells
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2014.03.017

•TACI-IgG treatment reduced B-cell percentage in lupus-like mice.•TACI-IgG treatment reduced anti-dsDNA antibody titer in lupus-like mice.•TACI-IgG treatment upregulated memory B cells in lupus-like mice.•TACI-IgG treatment up-regulated interleukin (IL)-15.•Combination of TACI-IgG and anti-IL-15 treated autoimmune diseases. 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.