Secondary lymphoid organs develop during embryogenesis or in the first few weeks after birth according to a highly coordinated series of interactions between newly emerging hematopoietic cells and immature mesenchymal or stromal cells. These interactions are orchestrated by homeostatic chemokines, cytokines and growth factors that attract hematopoietic cells to sites of future lymphoid organ development and promote their survival and differentiation. In turn, lymphotoxin-expressing hematopoietic cells trigger the differentiation of stromal and endothelial cells that make up the scaffolding of secondary lymphoid organs. Lymphotoxin signaling also maintains the expression of adhesion molecules and chemokines that govern the ultimate structure and function of secondary lymphoid organs. Here we describe the current paradigm of secondary lymphoid organ development and discuss the subtle differences in the timing, molecular interactions and cell types involved in the development of each secondary lymphoid organ. 2. The development of LTi cells from precursors in the fetal liver and their local differentiation into LTαβ-expressing cells requires the activities of cytokines, such as TRANCE or IL-7. IL-7 seems to be most important for the differentiation of LTi cells at mucosal sites, such as the Peyer's patches, while TRANCE is most important at sites of peripheral lymph node development.3. LTi cells are attracted to sites of lymphoid organ development by homeostatic chemokines, including CXCL13, CCL19 and CCL21. Like TRANCE and IL-7, these chemokines also maintain surface LTαβ expression on LTi cells.
4.The lymphotoxin signalling pathway plays a central role in the development of secondary lymphoid organs due to its ability to trigger mesenchymal cell differentiation, elicit homeostatic chemokine expression and to promote the differentiation of HEVs, stromal cells and dendritic cells.