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

TY - JOUR

T1 - Germinal center B cells recognize antigen through a specialized immune synapse architecture

AU - Nowosad, Carla R.

AU - Spillane, Katelyn M

AU - Tolar, Pavel

PY - 2016/7

Y1 - 2016/7

N2 - 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.

AB - 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.

U2 - 10.1038/ni.3458

DO - 10.1038/ni.3458

M3 - Article

SN - 1529-2908

VL - 17

SP - 870

EP - 877

JO - Nature Immunology

JF - Nature Immunology

ER -