Bone marrow stromal antigen 2 (BST2) is a host-restriction factor that plays multiple roles in the antiviral defense of innate immune responses, including the inhibition of viral particle release from virus-infected cells. BST2 may also be involved in the endothelial adhesion and migration of monocytes, but its importance in the immune system is still unclear. Immune cell adhesion and migration are closely related to the initiation of immune responses. In this study, we found that the expressions of the lymph node homing marker chemokine receptor 7 (CCR7) and an adhesion molecule intercellular adhesion molecule 1 (ICAM-1) in conventional dendritic cells (cDCs) were associated with BST2 expression. Interestingly, <i>Bst2</i>^-/- cDCs showed lower chemotactic ability, including velocity and accumulative distance toward chemokine ligand 19 (CCL19) gradient in vitro, compared to wild-type cDCs. <i>Bst2</i>^-/- cDCs also showed reduced migration and reduced retention capacity in draining lymph nodes in vivo. As a result, <i>Bst2</i>^-/- cDCs as antigen-presenting cells induced lower antigen-specific B cell and T cell responses compared to <i>Bst2</i>^+/+ cDCs. Notably, mice administered the influenza vaccine via <i>Bst2</i>^-/- cDCs exhibited substantially inefficient virus clearance compared to mice administered the <i>Bst2</i>^+/+ cDCs vaccine. Therefore, we propose that BST2, which plays a critical role in the effective migration and retention of cDCs, is involved in the development of optimal immunological effects in draining lymph nodes.