Germinal center B cells recognize antigen through a specialized immune synapse architecture
journal contributionposted on 2020-09-07, 11:28 authored by Carla R Nowosad, Katelyn M Spillane, Pavel Tolar
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.
AnimalsAntibody AffinityAntigen PresentationB-Lymphocyte SubsetsB-LymphocytesGerminal CenterHEK293 CellsHumansImmunologic MemoryImmunological SynapsesLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicNF-kappa BProtein Kinase C betaReceptors, Antigen, B-CellSignal TransductionT-Lymphocytes, Helper-InducerTolar FC001185Immunology1107 Immunology