Development of secondary lymphoid organs

Abstract

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.

Figure 1. General scheme of secondary lymphoid organ development

As noted in the text of the review, the details in the developmental pathways of Peyer’s patches and individual lymph nodes are often slightly different. Therefore, this scheme incorporates elements of both Peyer’s patch and lymph node development and outlines major steps that are likely to be in common in these pathways. Importantly, this scheme implies several events that are purely speculative. For example, it is unknown whether LTo cells are the direct precursors of mature stromal cells and follicular dendritic cells (FDCs). It is also unclear whether LTi cells and LTin cells are maintained in mature secondary lymphoid organs in adults.