Functional effects of TNF and lymphotoxin α1β2 on FDC-like cells

Recent studies suggest that tumor necrosis factor (TNF) family members such as TNF alpha and lymphotoxin alpha beta (LT alpha 1 beta 2) 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 LT alpha 1 beta 2 on expression of adhesion molecules and the production of cytokines and chemokines. TNF and LT alpha 1 beta 2 both increased the expression of VCAM-1 and ICAM-1 on FDC-LC, In addition, IL-4 with LT alpha 1 beta 2 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 LT alpha 1 beta 2. These two cytokines were present in FDC-LC supernatants by ELISA and increased following TNF and LT alpha 1 beta 2 stimulation. We also examined FDC-LC for chemokines, which affect B cells, including IL-8, SDF-1, MIP3 beta/ELC, and BCA-1/BLC, SDF-1 mRNA and protein were expressed by FDC-LC, and following stimulation with TNF and LT alpha 1 beta 2, decreases in both were observed. Therefore, TNF and LT alpha 1 beta 2 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, (C) 2000 Academic Press.