CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics
Copyright policy )CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics
AbstractContinuous 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.
Mice, Knockout, B-Lymphocytes, Mice, Inbred BALB C, Microscopy, Confocal, Cell Membrane, Green Fluorescent Proteins, Mice, Transgenic, Intercellular Adhesion Molecule-1, Lymphocyte Activation, Chemokine CXCL13, Actins, Lymphocyte Function-Associated Antigen-1, Mice, Inbred C57BL, Kinetics, Mice, Cell Movement, Cell Line, Tumor, Animals, Cells, Cultured, Cytoskeleton
Mice, Knockout, B-Lymphocytes, Mice, Inbred BALB C, Microscopy, Confocal, Cell Membrane, Green Fluorescent Proteins, Mice, Transgenic, Intercellular Adhesion Molecule-1, Lymphocyte Activation, Chemokine CXCL13, Actins, Lymphocyte Function-Associated Antigen-1, Mice, Inbred C57BL, Kinetics, Mice, Cell Movement, Cell Line, Tumor, Animals, Cells, Cultured, Cytoskeleton
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