Active tuning of synaptic patterns enhances immune discrimination

Abstract

Immune cells learn about their antigenic targets using tactile sense: during recognition, a highly organized yet dynamic motif, named immunological synapse, forms between immune cells and antigen-presenting cells (APCs). Via synapses, immune cells selectively extract recognized antigen from APCs by applying mechanical pulling forces generated by the contractile cytoskeleton. Curiously, depending on its stage of development, a B lymphocyte exhibits distinct synaptic patterns and uses force at different strength and timing, which appear to strongly impact its capacity of distinguishing antigen affinities. However, the mechanism by which molecular binding affinity translates into the amount of antigen acquisition remains an unsolved puzzle. We use a statistical-mechanical model to study how the experimentally observed synaptic architectures can originate from normal cytoskeletal forces coupled to lateral organization of mobile receptors, and show how this active regulation scheme, collective in nature, may provide a robust grading scheme that allows efficient and broad affinity discrimination essential for proper immune function.