Surface-bound antigen induces B-cell permeabilization and lysosome exocytosis facilitating antigen uptake and presentation to T-cells
AbstractB-cell receptor (BCR)-mediated antigen internalization and presentation are essential for humoral memory immune responses. Antigen encountered by B-cells is often tightly associated with the surface of pathogens and/or antigen-presenting cells. Internalization of such antigens requires myosin-mediated traction forces and extracellular release of lysosomal enzymes, but the mechanism triggering lysosomal exocytosis is unknown. Here we show that BCR-mediated high-affinity recognition of antigen tethered to beads or planar lipid-bilayers causes localized plasma membrane (PM) permeabilization, a process that requires BCR signaling and non-muscle myosin II activity. B-cell permeabilization triggers a PM repair response involving lysosomal exocytosis. B-cells transiently permeabilized by surface-associated antigen internalize more antigen than cells that remain intact, and higher affinity antigens that cause more B-cell permeabilization and lysosomal exocytosis are more efficiently presented to T-cells. Thus, PM permeabilization by surface-associated antigen triggers a lysosome-mediated B-cell resealing response, which provides the extracellular hydrolases that can facilitate antigen internalization and presentation.