title: Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-κB-B cell lymphoma 6 signaling.
abstract: 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.
authors: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jungtae
authors: J
authors: Kim
authors: Dong Wook
authors: DW
authors: Kim
authors: Wookyoung
authors: W
authors: Chang
authors: Jongseon
authors: J
authors: Choe
authors: Jihun
authors: J
authors: Kim
authors: Chan-Sik
authors: CS
authors: Park
authors: Kyuyoung
authors: K
authors: Song
authors: Inchul
authors: I
authors: Lee
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000276:immunology* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D051153:Wnt Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000276:immunology*; D000071818:Wnt-5a Protein
chemical_list: C084103:BCL6 protein, human; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse