CD24 induces apoptosis in human B cells via the glycolipid-enriched membrane domains/rafts-mediated signaling system

J Immunol. 2001 May 1;166(9):5567-77. doi: 10.4049/jimmunol.166.9.5567.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, B-Lymphocyte / biosynthesis
  • Antigens, Differentiation, B-Lymphocyte / immunology*
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Apoptosis / immunology*
  • Apoptosis Regulatory Proteins
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Biological Transport, Active / immunology
  • Burkitt Lymphoma / immunology
  • Burkitt Lymphoma / pathology
  • CD24 Antigen
  • Carrier Proteins / metabolism
  • Cell Fractionation
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Centrifugation, Density Gradient
  • Cholera Toxin / pharmacology
  • Glycosylphosphatidylinositols / metabolism*
  • Humans
  • Immune Sera / metabolism
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Membrane Glycoproteins*
  • Membrane Microdomains / metabolism
  • Membrane Microdomains / physiology*
  • Mitochondrial Proteins*
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / immunology*
  • Tumor Cells, Cultured / immunology
  • Tumor Cells, Cultured / metabolism
  • src-Family Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, B-Lymphocyte
  • Apoptosis Regulatory Proteins
  • Bik protein, mouse
  • CD24 Antigen
  • CD24 protein, human
  • Carrier Proteins
  • Glycosylphosphatidylinositols
  • Immune Sera
  • Membrane Glycoproteins
  • Mitochondrial Proteins
  • Receptors, Antigen, B-Cell
  • Cholera Toxin
  • lyn protein-tyrosine kinase
  • src-Family Kinases