| First Author | Kim J | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 1 | Pages | 182-9 |
| PubMed ID | 22124122 | Mgi Jnum | J:180820 |
| Mgi Id | MGI:5307945 | Doi | 10.4049/jimmunol.1102297 |
| Citation | Kim J, et al. (2012) Wnt5a is secreted by follicular dendritic cells to protect germinal center B cells via Wnt/Ca2+/NFAT/NF-kappaB-B cell lymphoma 6 signaling. J Immunol 188(1):182-9 |
| abstractText | 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-kappaB, 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-kappaB and BCL-6 in Ramos cells, supporting a role of beta-catenin-independent Wnt/Ca(2+)/NFAT/NF-kappaB-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. |
