Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses

Abstract

Subcapsular sinus macrophages (SSMs) play a key role in immune defense by forming immunological barriers that control the transport of antigens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal center reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro. Here, we used multicolor fluorescence microscopy to identify lymph node-derived SSMs in culture. We focused on the role of SSMs as antigen-presenting cells, and found that their actin cytoskeleton regulates the spatial organization and mobility of multivalent antigens (immune complexes [ICs]) displayed on the cell surface. Moreover, we determined that SSMs are mechanosensitive cells that respond to changes in extracellular matrix rigidity by altering the architecture of the actin cytoskeleton, leading to changes in cell morphology, membrane topography, and IC mobility. Changes to extracellular matrix rigidity also modulate actin remodeling by both SSMs and B cells when they form an immune synapse. This alters synapse duration but not IC internalization nor NF-κB activation in the B cell. Taken together, our data reveal that the mechanical microenvironment may influence B cell responses by modulating physical characteristics of antigen presentation by SSMs.