Figure 1.

Development and structure of secondary lymphoid structures. (a) During SLO development, the earliest instructive signal is from a neuronal cell that induces the local fibroblasts to upregulate CXCL13 and thus attract LTi cells. These cells express LTβ and instruct the local fibroblasts to become LTo cells that start producing chemokines for B cells (CXCL13), T cells and DCs (CCL19 and CCL21). At the same time, the fibroblasts upregulate cell adhesion molecules to allow LTis and recruited T and B cells to stick together. Local angiogenic growth factors are also made to allow the development of high endothelial venules (HEV), as well as afferent and efferent lymph vessels. (b) As a result, a well-organized structure with a separate B cell (blue) and T cell zone (red) is formed. This allows cell–cell contact at the appropriate time; and entry and exit of lymphocytes and antigen via the HEVs and lymphatics.