title: CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics.
abstract: Continuous migration of B cells at the follicle contrasts with their stable arrest after encounter with antigen. Two main ligand/receptor pairs are involved in these cell behaviors: the chemokine CXCL13/chemokine receptor CXCR5 and antigen/BCR. Little is known regarding the interplay between CXCR5 and BCR signaling in the modulation of B-cell dynamics and its effect on B-cell activation. We used a 2-dimensional model to study B-cell migration and antigen recognition in real time, and found that BCR signaling strength alters CXCL13-mediated migration, leading to a heterogeneous B-cell behavior pattern. In addition, we demonstrate that CXCL13/CXCR5 signaling does not impair BCR-triggered immune synapse formation and that CXCR5 is excluded from the central antigen cluster. CXCL13/CXCR5 signaling enhances BCR-mediated B-cell activation in at least 2 ways: (1) it assists antigen gathering at the synapse by promoting membrane ruffling and lymphocyte function-associated antigen 1 (LFA-1)-supported adhesion, and (2) it allows BCR signaling integration in motile B cells through establishment of LFA-1-supported migratory junctions. Both processes require functional actin cytoskeleton and non-muscle myosin II motor protein. Therefore, the CXCL13/CXCR5 signaling effect on shaping B-cell dynamics is an effective mechanism that enhances antigen encounter and BCR-triggered B-cell activation.
authors.affiliation: B Cell Dynamics Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Sáez de Guinoa
authors.forename: Laura
authors.initials: L
authors.lastname: Barrio
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
authors.forename: Yolanda R
authors.initials: YR
authors.lastname: Carrasco
mesh_terms: D000199:Actins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000276:immunology* / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D024462:Myosin Type II / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D054380:Receptors, CXCR5 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000199:Actins; C513179:CXCR5 protein, mouse; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; D016169:Lymphocyte Function-Associated Antigen-1; D011947:Receptors, Antigen, B-Cell; D054380:Receptors, CXCR5; D018799:Intercellular Adhesion Molecule-1; D049452:Green Fluorescent Proteins; D024462:Myosin Type II