title: Dynamic regulation of CD24 expression and release of CD24-containing microvesicles in immature B cells in response to CD24 engagement.
abstract: The glycophosphatidylinositol-anchored cell surface receptor CD24 (also called heat-stable antigen) promotes the apoptosis of progenitor and precursor B-lymphocytes. However, the immediate proximal events that occur after engagement of CD24 in B cells are not precisely understood. Using a bioinformatics analysis of mouse (Mus musculus) gene expression data from the Immunological Genome Project, we found that known vesicle trafficking and cellular organization genes have similar expression patterns to CD24 during B-cell development in the bone marrow. We therefore hypothesized that CD24 regulates vesicle trafficking. We first validated that antibody-mediated engagement of CD24 induces apoptosis in the mouse WEHI-231 cell line and mouse primary bone marrow-derived B cells. We next found that CD24 surface protein expression is rapidly and dynamically regulated in both WEHI-231 cells and primary immature B cells in response to engagement of CD24. The change in surface expression was not mediated by classical endocytosis or exocytosis. However, we found that CD24-bearing plasma membrane-derived extracellular microvesicles were released in response to CD24 engagement. Furthermore, in response to CD24 engagement we observed a clear exchange of CD24 between different populations of B cells. Hence, we show that engagement of CD24 in immature B cells results in a dynamic regulation of surface CD24 protein and a redistribution of CD24 within the population.
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: D Craig
authors.initials: DC
authors.lastname: Ayre
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Marcus
authors.initials: M
authors.lastname: Elstner
authors.affiliation: Cold-Ocean, Deep Sea Research Facility, Department of Ocean Sciences, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Smith
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Moores
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hogan
authors.affiliation: Department of Biochemistry, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Sherri L
authors.identifier: http://orcid.org/0000-0002-4289-4386
authors.initials: SL
authors.lastname: Christian
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051927:CD24 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000276:immunology* / Q000378:metabolism; D019295:Computational Biology; D030541:Databases, Genetic; D005434:Flow Cytometry; D053263:Gene Regulatory Networks; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000906:Antibodies; D051927:CD24 Antigen; C497890:Cd24a protein, mouse
keywords: B lymphocyte; CD24; apoptosis; bioinformatics; microvesicle