Craig Ayre - October 3

Characterization of the Extracellular Vesicles Released by B cells Following CD24 Stimulation

CD24 is expressed on many different cells and is known to influence a wide range of cell behaviours including differentiation, proliferation and apoptosis. On immature, developing B cells, engagement of CD24 using antibodies induces cell death. While downstream signalling pathways engaged by CD24 are known, much of the membrane-proximal signalling mechanism remains unclear. Understanding the mechanism of CD24 signalling in these cells may thus provide new understanding of how B cell development is regulated, and potential targets for treating B cell diseases such as leukemia or autoimmune disorders. We have recently discovered that CD24 induces B cells to release small extracellular vesicles (EV) from their plasma membrane. It is known that EV are capable of influencing cells with which they interact, however little is known about the overall composition of different EV populations. Therefore, we have undertaken a systematic characterization of CD24-EV for their RNA content, luminal proteome and their surface protein repertoire. The interior cargo carried by EV populations is heterogeneous and represent a spectrum of phenotypes rather than a single defined categorization. However, we found that EV populations released following CD24 stimulation have a distinct surface composition from EV released under basal conditions, as well as from their cells or origin. At present, the function of these EV remains unknown. Future analysis will identify the cells that interact with, as well as the function of CD24-EV on these target cells.

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Biochemistry

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