The recirculation of naive lymphocytes from the blood to LNs then back to the blood through the efferent lymphatics increases the likelihood that rare antigen-specific cells will encounter their specific antigen. Circulating lymphocytes enter the LNs at specialized postcapillary venules known as high endothelial venules (HEVs). Homing to HEVs is thought to occur in three steps. First, lymphocytes adhere loosely and roll along the endothelium. Next, they are activated by chemokines presented on endothelial proteoglycans. Finally, increased integrin affinity and avidity, triggered by chemokine signaling, leads to firm adhesion and arrest of the activated cells. The C-type lectin L-selectin is required for naive lymphocyte homing to peripheral LNs (1), and LNs are small and hypocellular in mice lacking this adhesion molecule (2). More specifically, L-selectin is the main receptor responsible for the rolling of these cells in HEVs. The rapid and...

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