A B cell actomyosin arc network couples integrin co-stimulation to mechanical force-dependent immune synapse formation

B-cell activation and immune synapse (IS) formation with membrane-bound
antigens are actin-dependent processes that scale positively with the
strength of antigen-induced signals. Importantly, ligating the B-cell
integrin, LFA-1, with ICAM-1 promotes IS formation when antigen is
limiting. Whether the actin cytoskeleton plays a specific role in
integrin-dependent IS formation is unknown. Here we show using
super-resolution imaging of mouse primary B cells that LFA-1: ICAM-1
interactions promote the formation of an actomyosin network that dominates
the B-cell IS. This network is created by the formin mDia1, organized into
concentric, contractile arcs by myosin 2A, and flows inward at the same
rate as B-cell receptor (BCR): antigen clusters. Consistently, individual
BCR microclusters are swept inward by individual actomyosin arcs. Under
conditions where integrin is required for synapse formation, inhibiting
myosin impairs synapse formation, as evidenced by reduced antigen
centralization, diminished BCR signaling, and defective signaling protein
distribution at the synapse. Together, these results argue that a
contractile actomyosin arc network plays a key role in the mechanism by
which LFA-1 co-stimulation promotes B-cell activation and IS formation.