Functional Effects of TNF and Lymphotoxin α1β2 on FDC-like Cells☆

Abstract Recent studies suggest that tumor necrosis factor (TNF) family members such as TNFα and lymphotoxin αβ (LTα1β2) are important in the development of follicular dendritic cells (FDCs) and maintenance of FDC function. In this study we used FDC-like cells (FDC-LC) cultured from normal human tonsil and investigated the effects of TNF and LTα1β2 on expression of adhesion molecules and the production of cytokines and chemokines. TNF and LTα1β2 both increased the expression of VCAM-1 and ICAM-1 on FDC-LC. In addition, IL-4 with LTα1β2 synergistically increased the expression of VCAM-1, but not ICAM-1. Cytokine IL-6 and IL-15 mRNAs were induced following stimulation with TNF and LTα1β2. These two cytokines were present in FDC-LC supernatants by ELISA and increased following TNF and LTα1β2 stimulation. We also examined FDC-LC for chemokines, which affect B cells, including IL-8, SDF-1, MIP3β/ELC, and BCA-1/BLC. SDF-1 mRNA and protein were expressed by FDC-LC, and following stimulation with TNF and LTα1β2, decreases in both were observed. Therefore, TNF and LTα1β2, which are produced by activated B cells, increased the expression of adhesion molecules and cytokines from FDC-LC, potentially providing key signals to support germinal center B cell survival and differentiation.