Germinal center B cells recognize antigen through a specialized immune synapse architecture

B cells can capture antigen to present to helper T cells. Tolar and colleagues show that germinal center B cells use a distinct synaptic architecture to capture antigen with higher mechanical forces than those of other B cells, which might provide the basis for affinity discrimination. 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.