TY - JOUR T1 - Surface-bound antigen induces B-cell permeabilization and lysosome exocytosis facilitating antigen uptake and presentation to T-cells JF - bioRxiv DO - 10.1101/2020.07.24.220418 SP - 2020.07.24.220418 AU - Fernando Y. Maeda AU - Jurriaan J. H. van Haaren AU - David B. Langley AU - Daniel Christ AU - Norma W. Andrews AU - Wenxia Song Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/27/2020.07.24.220418.abstract N2 - B-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 recognition of antigen tethered to beads, to planar lipid-bilayers or expressed on cell surfaces causes localized plasma membrane (PM) permeabilization, a process that requires BCR signaling and non-muscle myosin II. B-cell permeabilization triggers PM repair responses involving lysosomal exocytosis, and B-cells permeabilized by surface-associated antigen internalize more antigen than cells that remain intact. Higher affinity antigens cause more B-cell permeabilization and lysosomal exocytosis and are more efficiently presented to T-cells. Thus, PM permeabilization by surface-associated antigen triggers a lysosome-mediated B-cell resealing response, providing the extracellular hydrolases that facilitate antigen internalization and presentation.Competing Interest StatementThe authors have declared no competing interest. ER -