Physical extraction of antigen and information.

ABSTRACT

To respond and adapt, cells use surface receptors to sense environmental cues. While biochemical signal processing inside the cell is studied in depth, less is known about how physical processes during cell-cell contact impact signal acquisition. New experiments found that fast-evolving immune B cells in germinal centers (GCs) apply force to acquire antigen clusters prior to internalization, suggesting adaptive benefits of physical information extraction. We present a theory of stochastic antigen transfer and show that maximizing information gain via physical extraction can explain the dramatic phenotypic transition from naive to GC B cells-attenuated receptor signaling, enhanced force usage, and decentralized contact architecture. Our model suggests that binding-lifetime measurement and physical extraction serve as complementary modes of antigen recognition, greatly extending the dynamic range of affinity discrimination when combined. This physical-information framework further predicts that the optimal size of receptor clusters decreases as affinity improves, rationalizing the use of a multifocal synaptic pattern seen in GC B cells. By linking extraction dynamics to selection fidelity via discriminatory performance, we propose that cells may physically enhance information acquisition to sustain adaptive evolution.