Origin and Immunological Functions of Spleen Stromal Cells

The mammalian spleen is a peripheral lymphoid organ that plays a central role in host defense. Consequently, the lack of spleen is often associated with immunodeficiency and increased risk of overwhelming infections. Growing evidence suggests that non-hematopoietic stromal cells are central players in spleen development, organization, and immune functions. In addition to its immunological role, the spleen also provides a site for extramedullary hematopoiesis (EMH) in response to injuries. A deeper understanding of the biology of stromal cells is therefore essential to fully comprehend how these cells modulate the immune system during normal and pathological conditions. Here, we review the specificities of the different mouse spleen stromal cell subsets and complement the murine studies with human data when available. Embryonic mesenchymal progenitors within the splenic primordium (the clustering of cells from which the spleen develops) are the precursors of virtually all spleen stromal cell subsets, including follicular dendritic cells (FDCs), marginal reticular cells (MRCs), and fibroblastic reticular cells (FRCs). Spleen stromal cell subsets appear as central regulators of organ development and tissue regeneration, although the precise cellular and molecular determinants involved in these processes remain largely unknown. Distinct stromal cell subsets provide support for lymphocyte migration and locomotion and have unique functions involved in regulating adaptive immune responses.