Enhancement of terminal B lymphocyte differentiation in vitro by fibroblast-like stromal cells from human spleen

Stromal elements are major components of lymphoid tissues contributing to b oth tissue architecture and function. In this study we report on the phenot ype and function of fibroblast-like stromal cells obtained from human splee n. These cells express high levels of CD44 and ICAM-1 and moderate levels o f VLA-4, VCAM, CD40 and CD21. They fail to express endothelial, epithelial, lymphocyte and monocyte/macrophage markers. We show that these cells inter act with B cell blasts induced in vitro by anti-CD40 and anti-mu stimulatio n. As a result of these interactions both IL-6 and IgG secretion into cultu re medium is increased. The enhanced secretion of IgG is partly inhibited b y abolishing B cell blast-stromal cell contact or by anti-IL-6, anti-VCAM o r anti-CD49d antibodies. Our studies also suggest that the ability of strom al cells to promote B cell survival is most likely the underlying mechanism of the enhanced immunoglobulin secretion. Comparison of stromal cells from different lymphoid and non-lymphoid organs revealed that bone marrow- and spleen-derived stromal cells are the most effective in promoting B cell bla st differentiation.