Department of Rheumatology, First Hospital of Jilin University, Changchun 130021, China; Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing 100850, China.
Cell Immunol. 2014 May-Jun;289(1-2):140-4. doi: 10.1016/j.cellimm.2014.03.017. Epub 2014 Apr 12.
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.
临床试验表明，BAFF 抑制剂，如 atacicept（TACI-IgG）和 belimumab（抗 BAFF 抗体），虽然可以减少 CD20(+)幼稚 B 细胞和活化 B 细胞的数量，但不能减少记忆 B 细胞的数量。在本研究中，我们探讨了减少记忆 B 细胞数量的方法。首先，我们使用 TACI-IgG 治疗狼疮样小鼠。我们发现 TACI-IgG 能有效减少成熟 B 细胞的数量，从而控制狼疮样小鼠中抗 dsDNA 抗体的水平。此外，TACI-IgG 上调了狼疮样小鼠中的记忆 B 细胞。进一步的研究发现，TACI-IgG 在狼疮样小鼠中上调了 IL-15 的表达。因此，我们探索了 TACI-IgG 和抗 IL-15 抗体的联合应用，以了解它们对治疗狼疮样小鼠的效果。与单独使用 TACI-IgG 或抗 IL-15 相比，TACI-IgG 和抗 IL-15 抗体的联合应用能更有效地改善狼疮样小鼠的表型。该研究为 BAFF 和 IL-15 特异性治疗药物的临床应用提供了线索。
