The mechanism of CD24-mediated apoptosis in bone marrow-derived early B-cells.

Abstract

B cells are the antibody producing cells of the mammalian immune system and are formed through a differentiation and maturation process in the bone marrow. The glycophosphatidylinositol (GPI)-linked cell surface receptor CD24 causes apoptosis in the earliest B-cell developmental stages. As it has no transmembrane domain, the signal transduction mechanism of CD24 is not well understood and is the focus of this thesis. Using a bioinformatics approach, several genes were identified that are involved in apoptosis, cytoskeletal organization and endocytosis and whose pattern of expression tightly correlated with CD24. In addition, it was shown that extensive crosslinking of CD24 is required to mediate apoptosis in primary B-cells. Moreover, following crosslinking, CD24 protein is rapidly transported to the cell surface and then endocytosed. Lastly, it was observed that CD24 mediates homeotypic adhesion and is closely associated with cell-cell junctions. These data may provide new insight into the mechanism by which GPI-linked receptors activate intracellular signalling pathways.