Wnt5a Is Secreted by Follicular Dendritic Cells To Protect Germinal Center B Cells via Wnt/Ca2+/NFAT/NF-κB-B Cell Lymphoma 6 Signaling
Wnt5a Is Secreted by Follicular Dendritic Cells To Protect Germinal Center B Cells via Wnt/Ca2+/NFAT/NF-κB-B Cell Lymphoma 6 Signaling
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DOI：
10.4049/jimmunol.1102297
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发表时间：
2012-01-01
影响因子：
4.4
通讯作者：
Lee, Inchul
中科院分区：
文献类型：
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作者：
Kim, Jungtae;Kim, Dong Wook;Lee, Inchul
滤泡树突状细胞（FDCs）保护生发中心（GC） B细胞免于快速凋亡，使其存活和成熟。在本文中，我们发现fdc通常产生和分泌Wnt5a来保护GC B细胞。Wnt5a的产生被polyI:C上调。纯化的Wnt5a以剂量依赖性的方式保护GC B细胞免于凋亡。GC B细胞受FDC共培养或条件培养基的保护，抗Wnt5a Ab明显抑制这种保护作用，提示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/Ca2+信号在GC B细胞存活中的作用。Wnt5a和钙离子载体可迅速激活NFATc1、NFATc2、NF-kappa B和B细胞淋巴瘤6 (BCL-6)，并上调GC B和Ramos细胞中CD40的表达，而p53和JNK未上调或激活。环孢素A抑制Wnt5a和钙诱导的拉莫斯细胞NF-kappa B和BCL-6的激活，支持β -连环蛋白独立的Wnt/Ca2+/NFAT/NF-kappa B-BCL-6信号的作用。我们的数据支持Wnt5a是GC B细胞的一种新的生存因子，可能是B细胞免疫调节的潜在靶点。中华免疫学杂志，2012,18(8):582 - 589。
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/Ca2+ signaling in the GC B cell survival. Wnt5a and calcium ionophore activate NFATc1, NFATc2, NF-kappa B, 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-kappa B and BCL-6 in Ramos cells, supporting a role of beta-catenin-independent Wnt/Ca2+/NFAT/NF-kappa B-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. The Journal of Immunology, 2012, 188: 182-189.