CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system.
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.
Suzuki
T
T
Department of Pathology, National Children's Medical Research Center, Tokyo, Japan.
Kiyokawa
N
N
Taguchi
T
T
Sekino
T
T
Katagiri
Y U
YU
Fujimoto
J
J
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001693:Biological Transport, Active / Q000276:immunology; D002051:Burkitt Lymphoma / Q000276:immunology / Q000473:pathology; D051927:CD24 Antigen; D002352:Carrier Proteins / Q000378:metabolism; D002458:Cell Fractionation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D002772:Cholera Toxin / Q000494:pharmacology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins; D021962:Membrane Microdomains / Q000378:metabolism / Q000502:physiology*; D024101:Mitochondrial Proteins; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D051017:Apoptosis Regulatory Proteins; C111741:Bik protein, mouse; D051927:CD24 Antigen; C497889:CD24 protein, human; D002352:Carrier Proteins; D017261:Glycosylphosphatidylinositols; D007106:Immune Sera; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011947:Receptors, Antigen, B-Cell; D002772:Cholera Toxin; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases