Expression of APRIL in the FL tumor microenvironment. (A) Expression of APRIL, CD20, CD3, and CD68 was determined by immunohistochemistry in FL (n = 10). A representative case of FL, grade 1, is shown. APRIL immunoreactivity is seen within neoplastic follicles ([], top left panel) using an APRIL-specific antibody, but not an isotype control. Higher magnification (top right panel) shows the staining surrounding abnormal small lymphocytes within the neoplastic follicles. (B) Cells from normal tonsilar tissue (Ton) or FL patient specimens (n = 5) were cultured for 7 days, and supernatants were collected and assessed for APRIL by ELISA. (C) Expression of APRIL by LCL, PB mononuclear cells, CD19+ FL cells, and HS.5 stromal cells was determined by Western blot using APRIL-specific antibody. (D) Karpas cells were cultured alone or cocultured with irradiated HS.5 cells in the presence of TACI-Fc (5 μg/mL) or control-Fc (5 μg/mL), and growth was assessed by thymidine incorporation. Mean (± SDs) from 6 determinations obtained in 2 separate experiments are shown.