The role of extracellular vesicles in B cell development and function

In cellular microenvironments such as the bone marrow (where B cell development occurs), cells can communicate with proximal and/or distal cells via secretion of extracellular vesicles (EVs). EVs are membrane-encapsulated nanosized particles that carry bioactive cargo such as proteins, nucleic acids and lipids. Recent research in the Christian Lab showed that engagement of the glycophosphatidylinositol (GPI)-anchored surface receptor CD24 on immature murine B lymphoma cell line WEHI 231 induced the release of CD24-bearing EVs (CD24-EV). However, the role of EVs including CD24-EV in B cell development and function is unknown. We hypothesize that EVs facilitate the exchange of information between cells in the bone marrow, thereby regulating B cell development and function. To help us understand the mechanism and function of EV release and uptake in B cells, we have tracked EV release and uptake between fluorescently labelled WEHI cells (WEHI 231-GFP and WEHI 303-Tomato), using multi-color flow cytometry. Our data shows that stimulation of CD24 on donor cells followed by incubation with recipient cells induces CD24-EV transfer, based on analysis of both lipid and protein to recipient cells. We determined that protein transferred by CD24-EV is functional in the recipient cells. Furthermore, we determined that other surface receptors can induce EV release and functional protein transfer. In our future work, we will identify the types of receptors necessary for EV uptake, and the stage of B cell development when EV uptake can occur. Consequently, our research will broaden the understanding of EV based cell-cell communication, and its role in normal B cell development.