Fibroblastic reticular cells of the peripheral lymphoid organs: Unique features of a ubiquitous cell type

The highly ordered structure in peripheral lymphoid tissues is maintained by continuous interactions between their hemopoietic and stromal components. The main reticular cell type, fibroblastic reticular cells (FRCs) emerged as a considerably heterogeneous group of the stroma. These cells have diverse roles beyond architectural scaffolding. Their functions include the formation of nests for recirculating lymphocytes with subset-preference and a dynamic filtration system for facilitating encounter between antigen, antigen-presenting cells and antigen-receptor bearing cells. FRCs are influenced by lymphocyte-derived morphogenic signals and factors necessary for lymphoid tissue formation and lymphocyte homeostasis. Moreover, FRCs may also interact with other stromal elements during both lymphoid organ development and immune responses. FRCs are profoundly affected by pathogens, which may limit the lymphoid cells’ capacity to establish efficient protection. This review focuses on the ontogenic, phenotypic and functional complexities of FRCs and their role in the stromal rearrangement of lymphoid tissues.