The Network of Fibroblastic Reticular Cells in the Lymph Node:Functional Framework for Immune Surveillance

Lymph nodes (LNs) are crucial organs for triggering adaptive immune responses, and are localized at key places in the network of the lymphatic vascular system in order to filter tissue fluid exudates containing antigens effectively. Within the LN, immune cells are strategically compartmentalized to form a unique tissue architecture that is mechanically and functionally supported by several types of stromal cells of mesenchymal origin. In particular, one of the stromal cell types known as fibroblastic reticular cells (FRCs) produces extracellular matrix fibers and constructs an elaborate network of reticulum that serves as a foothold for immune cells' movement. This network of matrix fibers ensheathed by FRCs also functions as a transport system for low molecular weight materials, including lymph-borne soluble antigens. In addition, FRCs potentially control the localization and homeostasis of immune cells by producing various factors such as adhesion molecules, chemokines, and cytokines. Therefore, this type of less-understood stromal cell component in the LN plays a central role in the spatiotemporal regulation of adaptive immune surveillance.