Proposed role for ICAM-1 and ICAM-2 during lymphocyte trafficking to and within PLNs. Blood-borne lymphocytes undergo rapid firm arrest in a largely ICAM-1 and ICAM-2-dependent manner, with a residual contribution of VCAM-1, in particular in the smallest HEVs (A). Approximately one-third of adherent T cells subsequently crawl on the luminal HEV surface, independent of the direction of the blood flow, in an ICAM-1-dependent manner (B). The rapid transmigration event (∼ 1.5 minutes) can occur in the absence of endothelial ICAM-1 and ICAM-2 (C), and is followed in the majority of cells by “perivascular trapping” of the cells, perhaps because of entanglement with the basement membrane underlying the HEV and due to the cuff of surrounding fibroblastic stromal cells (D). Parenchymal ICAM-1 supports T- and B-cell motility through increased speed and directionality, presumably by allowing loose anchorage of scanning lymphocytes to the stromal network for guidance. Lymphocyte motility driven through chemokines and other factors can nonetheless take place efficiently in absence of ICAM-1 and α4 integrin ligands (E). HEC indicates high endothelial cell; BM, basement membrane; TRC, T-cell reticular zone cell; and FDC, follicular dendritic cell.