Abstract
The glycosylphosphatidylinositol-anchored CD24 protein is a B cell differentiation Ag that is expressed on mature resting B cells but disappears upon Ag stimulation. We used Burkitt's lymphoma (BL) cells, which are thought to be related to germinal center B cells, to examine the biological effect of Ab-mediated CD24 cross-linking on human B cells and observed 1) induction of apoptosis in BL cells mediated by cross-linking of CD24; and 2) synergism between the cross-linking of CD24 and that of the B cell receptor for Ag in the effect on apoptosis induction. We also observed activation of mitogen-activated protein kinases following CD24 cross-linking, suggesting that CD24 mediates the intracellular signaling that leads to apoptosis in BL cells. Although CD24 has no cytoplasmic portion to transduce signals intracellularly, analysis of biochemically separated glycolipid-enriched membrane (GEM) fractions indicated enhanced association of CD24 and Lyn protein tyrosine kinase in GEM as well as increased Lyn kinase activity after CD24 cross-linking, suggesting that CD24 mediates intracellular signaling via a GEM-dependent mechanism. Specific microscopic cocapping of CD24 and Lyn, but not of other kinases, following CD24 cross-linking supported this idea. We further observed that apoptosis induction by cross-linking is a common feature shared by GEM-associated molecules expressed on BL cells, including GPI-anchored proteins and glycosphingolipids. CD24-mediated apoptosis in BL cells may provide a model for the cell death mechanism initiated by GEM-associated molecules, which is closely related to B cell receptor for Ag-mediated apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Antibodies, Monoclonal / metabolism
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Antigens, CD / biosynthesis
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Antigens, CD / immunology*
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Antigens, CD / metabolism
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Antigens, Differentiation, B-Lymphocyte / biosynthesis
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Antigens, Differentiation, B-Lymphocyte / immunology*
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Antigens, Differentiation, B-Lymphocyte / metabolism
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Apoptosis / immunology*
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Apoptosis Regulatory Proteins
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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Biological Transport, Active / immunology
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Burkitt Lymphoma / immunology
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Burkitt Lymphoma / pathology
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CD24 Antigen
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Carrier Proteins / metabolism
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Cell Fractionation
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Centrifugation, Density Gradient
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Cholera Toxin / pharmacology
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Glycosylphosphatidylinositols / metabolism*
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Humans
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Immune Sera / metabolism
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Intracellular Fluid / immunology
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Intracellular Fluid / metabolism
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Membrane Glycoproteins*
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Membrane Microdomains / metabolism
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Membrane Microdomains / physiology*
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Mitochondrial Proteins*
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Receptors, Antigen, B-Cell / immunology
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Receptors, Antigen, B-Cell / metabolism
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Signal Transduction / immunology*
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Tumor Cells, Cultured / immunology
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Tumor Cells, Cultured / metabolism
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src-Family Kinases / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation, B-Lymphocyte
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Apoptosis Regulatory Proteins
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Bik protein, mouse
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CD24 Antigen
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CD24 protein, human
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Carrier Proteins
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Glycosylphosphatidylinositols
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Immune Sera
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Membrane Glycoproteins
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Mitochondrial Proteins
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Receptors, Antigen, B-Cell
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Cholera Toxin
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lyn protein-tyrosine kinase
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src-Family Kinases