RT Journal Article SR Electronic T1 Stepwise transmigration cascade of T and B cells through the perivascular channel in lymph node high endothelial venules JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.12.20.423079 DO 10.1101/2020.12.20.423079 A1 Kibaek Choe A1 Jieun Moon A1 Soo Yun Lee A1 Eunjoo Song A1 Ju Hee Back A1 Joo-Hye Song A1 Young-Min Hyun A1 Kenji Uchimura A1 Pilhan Kim YR 2020 UL http://biorxiv.org/content/early/2020/12/21/2020.12.20.423079.abstract AB High endothelial venules (HEVs) effectively recruit circulating lymphocytes from the blood to lymph nodes. HEVs have endothelial cells (ECs) and perivascular sheaths consisting of fibroblastic reticular cells (FRCs). Many studies have characterized the multiple steps of lymphocyte migration interacting with ECs at the luminal side of HEVs. However, post-luminal migration steps are not well elucidated. Herein, we performed intravital imaging to investigate post-luminal T and B cell migration, consisting of trans-EC migration, crawling in the perivascular channel (a narrow space between ECs and FRCs) and trans-FRC migration. The post-luminal migration of T cells occurred in a PNAd-dependent manner. Remarkably, we found hot spots for the trans-EC and trans-FRC migration of T and B cells. Interestingly, T and B cells preferentially shared trans-FRC migration hot spots but not trans-EC migration hot spots. Furthermore, the trans-FRC T cell migration was confined to fewer sites than trans-EC T cell migration, and trans-FRC migration of T and B cells preferentially occurred at FRCs covered by CD11c+ dendritic cells in HEVs. These results suggest that HEV ECs and FRCs with perivascular DCs delicately regulate T and B cell entry into lymph nodes.Competing Interest StatementThe authors have declared no competing interest.