Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
J Immunol. 2012 Jan 1;188(1):182-9. doi: 10.4049/jimmunol.1102297. Epub 2011 Nov 28.
Follicular dendritic cells (FDCs) protect germinal center (GC) B cells from rapid apoptosis to allow their survival and maturation. In this article, we show that FDCs normally produce and secrete Wnt5a to protect GC B cells. Wnt5a production is upregulated by polyI:C. Purified Wnt5a protects GC B cells from apoptosis in a dose-dependent manner. GC B cells are protected by FDC coculture or conditioned medium, and the protection is inhibited significantly by anti-Wnt5a Ab, suggesting a major role of Wnt5a in the FDC-mediated GC B cell protection. A calcium chelator BAPTA-AM blocks the Wnt5a-mediated GC B cell protection, implying a role of Wnt/Ca(2+) signaling in the GC B cell survival. Wnt5a and calcium ionophore activate NFATc1, NFATc2, NF-κB, and B cell lymphoma 6 (BCL-6) promptly and upregulate CD40 expression in GC B and Ramos cells, whereas p53 and JNK are not upregulated or activated. Cyclosporine A inhibits the Wnt5a and calcium-induced activation of NF-κB and BCL-6 in Ramos cells, supporting a role of β-catenin-independent Wnt/Ca(2+)/NFAT/NF-κB-BCL-6 signaling. Our data support that Wnt5a is a novel survival factor for GC B cells and might be a potential target for the regulation of B cell immunity.
滤泡树突状细胞（FDC）保护生发中心（GC）B 细胞免受快速凋亡，以允许它们存活和成熟。在本文中，我们表明 FDC 通常产生和分泌 Wnt5a 以保护 GC B 细胞。Wnt5a 的产生可被聚肌苷酸（polyI:C）上调。纯化的 Wnt5a 以剂量依赖的方式保护 GC B 细胞免于凋亡。FDC 共培养或条件培养基可保护 GC B 细胞，而抗 Wnt5a Ab 可显著抑制保护作用，表明 Wnt5a 在 FDC 介导的 GC B 细胞保护中起主要作用。钙螯合剂 BAPTA-AM 阻断 Wnt5a 介导的 GC B 细胞保护，暗示 Wnt/Ca（2+）信号在 GC B 细胞存活中起作用。Wnt5a 和钙离子载体迅速激活 NFATc1、NFATc2、NF-κB 和 B 细胞淋巴瘤 6（BCL-6），并上调 GC B 和 Ramos 细胞中的 CD40 表达，而 p53 和 JNK 未上调或激活。环孢素 A 抑制 Wnt5a 和钙诱导的 Ramos 细胞中 NF-κB 和 BCL-6 的激活，支持β-连环蛋白非依赖性 Wnt/Ca（2+）/NFAT/NF-κB-BCL-6 信号传导。我们的数据支持 Wnt5a 是 GC B 细胞的一种新型存活因子，并且可能是调节 B 细胞免疫的潜在靶标。
