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Craig Ayre - Jan 18

THE MECHANISM OF CD24-MEDIATED APOPTOSIS IN MOUSE PRO-B CELLS

The regulation of early B cell development is essential to allow the generation of functional, non-autoreactive B cells. This process occurs in the bone marrow and starts when stem cells become committed to the B-cell lineage and then undergo a progressive differentiation into mature cells capable of producing antibodies. Stimulation of CD24, a glycophosphatidylinositol (GPI)-linked cell surface receptor, causes apoptosis in the earliest B-cell developmental stages, termed progenitor (pro-) and precursor (pre-) B cells. As it has no transmembrane domain, the mechanism by which CD24 communicates with the interior of the cell, as well as the downstream signalling cascade that results in apoptosis, is not well understood. Our lab is currently working to determine how CD24 communicates with the interior of the cell and subsequently triggers apoptosis. We have used microarray data from the Immunological Genome Project to identify potential effectors of CD24-mediated apoptosis through co-expression analysis and subsequent biological validation. These data have important implications for understanding how CD24 can mediate apoptosis in pro-B cells, but may also provide new insight into the mechanism by which GPI-linked receptors activate intracellular signalling pathways.

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