Surface-associated antigen induces permeabilization of primary mouse B-cells and lysosome exocytosis facilitating antigen uptake and presentation to T-cells

eLife

Fernando Y Maeda¹  Wenxia Song¹  Jurriaan JH van Haaren¹  Norma W Andrews¹  David B Langley²  Daniel Christ³ 

[1] Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, United States;Immunology Division, Garvan Institute of Medical Research, Darlinghurst, Australia;Immunology, Garvan Institute of Medical Research, Darlinghurst/Sydney, Australia;

关键词: B cell;    surface antigen;    resealing;    lysosome;    endocytosis;    antigen presentation;    Mouse;   

DOI  :  10.7554/eLife.66984

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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 activity. 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.

【 授权许可】

CC BY