B-cells need to internalize antigen from antigen-presenting cells (APCs) to enable the expansion of high-affinity antibody-producing B-cell clones. Two mechanisms have been suggested for antigen extraction: enzymatic degradation of the antigen or a physical pull on it by the B-cell. Spillane and Tolar develop tools revealing that mechanical extraction dominates and is dependent on the physical properties of the APC membrane (J. Cell Biol. 216, 217–230; 2017)

The authors design a DNA-based fluorescent sensor that reports on mechanical versus enzymatic antigen extraction. Tethering antigen to substrates with mobility and stiffness shows that the type of extraction depends on the physical properties of the substrate. Combining this sensor with one that releases the antigen at a certain level of force applied by the B-cell demonstrates that mechanical extraction dominates. Further, stiff substrates promote selection of higher-affinity antigen, whereas flexible substrates mediate more efficient antigen extraction. They turn to experiments in which the sensor is loaded onto APCs relevant in vivo — follicular dendritic cells (FDCs) and dendritic cells (DCs). Atomic force microscopy shows that DCs have a more flexible plasma membrane than FDCs, and indeed DCs allow antigen extraction at weak forces, whereas FDCs promote better affinity discrimination, the latter dependent on actin.

These elegant experiments highlight the role of physical forces in antibody internalization. How forces are sensed by B-cells remains to be investigated.