title: Lipid raft-dependent plasma membrane repair interferes with the activation of B lymphocytes.
abstract: Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca(2+)-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca(2+)-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR-lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte-mediated immune responses.
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Heather
authors.initials: H
authors.lastname: Miller
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Thiago
authors.initials: T
authors.lastname: Castro-Gomes
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Matthias
authors.initials: M
authors.lastname: Corrotte
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Christina
authors.initials: C
authors.lastname: Tam
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Timothy K
authors.initials: TK
authors.lastname: Maugel
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742.
authors.forename: Norma W
authors.initials: NW
authors.lastname: Andrews
authors.affiliation: Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742 wenxsong@umd.edu.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Song
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D008213:Lymphocyte Activation; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000378:metabolism
chemical_list: D002118:Calcium