Department of Pathology, Asan Medical Centre, University of Ulsan College of Medicine, Seoul, Korea.
Immunology. 2010 Aug;130(4):536-44. doi: 10.1111/j.1365-2567.2010.03252.x. Epub 2010 Mar 16.
The germinal centre (GC) is a specialized microenvironment where high-affinity antibodies are produced through hypermutation and isotype switching. Follicular dendritic cells (FDCs) are the stromal cells of the GC. The timely expansion and establishment of an FDC network is essential for a protective GC reaction; however, only a few factors modulating FDC development have been recognized. In this study, we report that interleukin-15 (IL-15) enhances human primary FDC proliferation and regulates cytokine secretion. The FDCs express IL-15 receptor complexes for IL-15 signal transduction as well as for specific binding. Moreover, the secretion of chemokines CCL-2, CCL-5, CXCL-5 and CXCL-8 was reduced by blocking IL-15 signalling while the secretion of other cytokines, and the expression of CD14, CD44, CD54 (ICAM-1) and CD106 (VCAM-1) proteins remained unchanged. These results suggest that IL-15 plays a crucial role in the development of FDC networks during GC reaction, offering a new target for immune modulation.
生发中心(GC)是一个专门的微环境,其中通过超突变和同种型转换产生高亲和力抗体。滤泡树突状细胞(FDC)是 GC 的基质细胞。及时扩展和建立 FDC 网络对于保护性 GC 反应至关重要;然而,只有少数调节 FDC 发育的因素得到了认可。在这项研究中,我们报告白细胞介素 15(IL-15)增强了人原代 FDC 的增殖并调节细胞因子的分泌。FDC 表达 IL-15 受体复合物,用于 IL-15 信号转导以及特异性结合。此外,阻断 IL-15 信号会降低趋化因子 CCL-2、CCL-5、CXCL-5 和 CXCL-8 的分泌,而其他细胞因子的分泌以及 CD14、CD44、CD54(ICAM-1)和 CD106(VCAM-1)蛋白的表达保持不变。这些结果表明,IL-15 在 GC 反应期间 FDC 网络的发育中发挥着关键作用,为免疫调节提供了一个新的靶点。