B cells use mechanical energy to distinguish affinity and speed up adaptation

Generation of potent antibodies relies on positive selection of germinal center (GC) B cells expressing high affinity receptors. Effective selection during the rapid evolutionary process called affinity maturation requires efficient ranking of affinity. Yet, the mechanism by which affinity discrimination is achieved and how it affects B cell evolution remains unclear. Growing evidence shows that B cells use mechanical forces to actively extract antigens from the surface of antigen-presenting cells. Here we study the stochastic process of antigen extraction using theory and simulations. We find that application of mechanical force alters the energy landscape of molecular interactions and consequently extends the range of distinguishable affinities. Integrating this extraction model on the molecular scale with GC dynamics on the population level, we demonstrate that exertion of cytoskeletal forces for antigen extraction can accelerate the rate of affinity maturation.