Previously, we described the characteristics of a cell line that is derived from a low density fraction of human tonsillar cells and, on the basis of a number of criteria, is related to follicular dendritic cells (FDC). This line, FDC-1, binds B lymphocytes and not T lymphocytes, and promotes anti-Ig- or anti-CD40-induced B cell proliferation. In this work, we show that culturing B cells with small numbers of FDC-1 cells leads to significant production of IL-6 and of both IgM and IgG. As few as 50 to 100 FDC-1 augmented B cell IgM production by 10- to 100-fold. Although fixed FDC-1 cells, unlike live FDC-1 cells, do not stimulate Ig production, cell contact is not required for all FDC-dependent Ig production. Supernatants from cultured FDC-1 cells can also stimulate B cells to produce IgM, suggesting that FDC produce a soluble B cell stimulating factor(s). Augmentation of FDC-dependent IgM production by either IL-6 or IL-7 and augmentation of FDC-dependent IgG production by IL-4 does require FDC-1 cells to be in contact with B cells. When the effects of FDC-1 cells were compared with those of epithelial cell lines and human foreskin fibroblasts (HFF), both FDC-1 cells and HFF induced B cells to produce IgM. FDC-1, unlike HFF, were positive for CD40, CD54, CD73, CD74, and nerve growth factor receptor (NGFR), and unlike HFF, but like certain stromal cells, FDC-1 cells also expressed smooth muscle actin, and a novel marker for stromal cells, BST-1. The possible relationship of FDC-1 cells and FDC in general to a fibroblast/stromal cell lineage is discussed.