High endothelial venules as traffic control points maintaining lymphocyte population homeostasis in lymph nodes

Millions of lymphocytes enter and exit mammal lymph nodes (LNs) each day, accessing the parenchyma via high endothelial venules (HEVs) and egressing via lymphatics. Despite this high rate of cellular flux and the many entry and exit sites within a given LN, the number of lymphocytes present in a resting LN is extraordinary stable over time, raising the question of how this steady-state is maintained. Here we have examined the anatomic details of lymphocyte movement in HEVs, finding that HEVs create pockets within which lymphocytes reside for several minutes before entering the LN proper. The function of these pockets was revealed in experiments performed under conditions in which lymphocyte egress from the LN was compromised by any of several approaches. Under such conditions, the HEVs pockets behaved as "waiting areas" in which lymphocytes were held until space was made available to them for entry into the parenchyma. Thus, rather than being simple entry ports, HEVs act as gatekeepers able to stack, hold and grant lymphocytes access to LN parenchyma in proportion to the rate of lymphocyte egress from the LN, enabling the LN to maintain a constant steady-state cellularity while supporting the extensive cellular trafficking necessary for repertoire scanning.