CXCL13 is an arrest chemokine for B cells in high endothelial venules.

Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13-/- mice and that B-cell adhesion is substantially restored in CXCL13-/- HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy.

Molecular determinants controlling homeostatic recirculation and tissue-specific trafficking of lymphocytes.

The homeostasis of the immune system is maintained by the recirculation of naïve lymphocytes through the secondary lymphoid tissues, such as the lymph nodes, Peyer's patches, and spleen. Upon insult by pathogens or antigens, lymphocytes become activated, and the regulated trafficking of these cells results in the integration of systemic and regional immune responses. The exquisite specificity of such lymphocyte trafficking is determined by tissue-specific guidance signals expressed by the endothelial cells of postcapillary venules, combined with counterreceptors expressed by the circulating lymphocytes.

Lymphocyte binding to MAdCAM-1 via alpha4beta7 integrin activates a signal transduction pathway involving tyrosine phosphorylation of paxillin and p105(Cas-L).

Alpha4beta7 integrin mediates lymphocyte trafficking to mucosal lymphoid organs by interacting with the mucosal vascular addressin MAdCAM-1. While the structural basis for the alpha4beta7 integrin-MAdCAM-1 interaction has been well characterized, less is known about the signal transduction pathways that regulate the alpha4beta7 integrin-mediated lymphocyte interaction with MAdCAM-1-expressing endothelial cells. Here we demonstrate that ligation of alpha4beta7 integrin with MAdCAM-1 induces a prominent tyrosine phosphorylation of paxillin and a 105-kDa protein (p105) that is reactive with an anti-p130(Cas) antibody, in the mouse T-cell line TK-1.