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

Nat Immunol. 2016 Jul;17(7):870-7. doi: 10.1038/ni.3458. Epub 2016 May 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Affinity
  • Antigen Presentation
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocytes / immunology*
  • Germinal Center / immunology*
  • HEK293 Cells
  • Humans
  • Immunologic Memory
  • Immunological Synapses*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Protein Kinase C beta / metabolism
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • NF-kappa B
  • Receptors, Antigen, B-Cell
  • Protein Kinase C beta