title: Germinal center B cells recognize antigen through a specialized immune synapse architecture.
abstract: B cell activation is regulated by B cell antigen receptor (BCR) signaling and antigen internalization in immune synapses. Using large-scale imaging across B cell subsets, we found that, in contrast with naive and memory B cells, which gathered antigen toward the synapse center before internalization, germinal center (GC) B cells extracted antigen by a distinct pathway using small peripheral clusters. Both naive and GC B cell synapses required proximal BCR signaling, but GC cells signaled less through the protein kinase C-β-NF-κB pathway and produced stronger tugging forces on the BCR, thereby more stringently regulating antigen binding. Consequently, GC B cells extracted antigen with better affinity discrimination than naive B cells, suggesting that specialized biomechanical patterns in B cell synapses regulate T cell-dependent selection of high-affinity B cells in GCs.
authors.affiliation: Laboratory of Activation of Immune Receptors, Francis Crick Institute, Mill Hill Laboratory, London, UK.
authors.forename: Carla R
authors.initials: CR
authors.lastname: Nowosad
authors.affiliation: Laboratory of Activation of Immune Receptors, Francis Crick Institute, Mill Hill Laboratory, London, UK.|Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, UK.
authors.forename: Katelyn M
authors.initials: KM
authors.lastname: Spillane
authors.affiliation: Laboratory of Activation of Immune Receptors, Francis Crick Institute, Mill Hill Laboratory, London, UK.|Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, UK.
authors.forename: Pavel
authors.identifier: 0000-0003-4693-7299
authors.initials: P
authors.lastname: Tolar
mesh_terms: D000818:Animals; D000915:Antibody Affinity; D017951:Antigen Presentation; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D057809:HEK293 Cells; D006801:Humans; D007156:Immunologic Memory; D054992:Immunological Synapses; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D064546:Protein Kinase C beta / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D064546:Protein Kinase C beta