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 differen tiation 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) synergis m 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 mitoge n-activated protein kinases following CD24 cross-linking, suggesting that C D24 mediates the intracellular signaling that leads to apoptosis in BL cell s. Although CD24 has no cytoplasmic portion to transduce signals intracellu larly, analysis of biochemically separated glycolipid-enriched membrane (GE M) fractions indicated enhanced association of CD24 and Lyn protein tyrosin e kinase in GEM as well as increased Lyn kinase activity after CD24 cross-l inking, suggesting that CD24 mediates intracellular signaling via a GEM-dep endent mechanism. Specific microscopic cocapping of CD24 and Lyn, but not o f other kinases, following CD24 cross-linking supported this idea. We furth er observed that apoptosis induction by cross-linking is a common feature s hared by GEM-associated molecules expressed on BL cells, including GPI-anch ored proteins and glycosphingolipids. CD24-mediated apoptosis in BL cells m ay provide a model for the cell death mechanism initiated by GEM-associated molecules, which is closely related to B cell receptor for Ag-mediated apo ptosis.