title: Vinculin arrests motile B cells by stabilizing integrin clustering at the immune synapse.
abstract: Lymphocytes use integrin-based platforms to move and adhere firmly to the surface of other cells. The molecular mechanisms governing lymphocyte adhesion dynamics are however poorly understood. In this study, we show that in mouse B lymphocytes, the actin binding protein vinculin localizes to the ring-shaped integrin-rich domain of the immune synapse (IS); the assembly of this platform, triggered by cognate immune interactions, is needed for chemokine-mediated B cell motility arrest and leads to firm, long-lasting B cell adhesion to the APC. Vinculin is recruited early in IS formation, in parallel to a local phosphatidylinositol (4,5)-bisphosphate wave, and requires spleen tyrosine kinase activity. Lack of vinculin at the IS impairs firm adhesion, promoting, in turn, cell migration with Ag clustered at the uropod. Vinculin localization to the B cell contact area depends on actomyosin. These results identify vinculin as a major controller of integrin-mediated adhesion dynamics in B cells.
authors.affiliation: B Cell Dynamics Laboratory, Department of Immunology and Oncology, Centro Nacional de Biotecnología-Consejo Superior de Investigaciones Científicas, Madrid E-28049, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Saez de Guinoa
authors.forename: Laura
authors.initials: L
authors.lastname: Barrio
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Carrasco
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002448:Cell Adhesion / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D054992:Immunological Synapses / Q000276:immunology / Q000378:metabolism*; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016596:Vinculin / Q000276:immunology / Q000378:metabolism*
chemical_list: D016023:Integrins; D016596:Vinculin