An ex vivo and in vitro investigation of extracellular vesicle interactions with B cells of Macaca nemestrina and humans

Extracellular vesicles may modify recipient cell behavior through multiple mechanisms, including interacting with the cell surface or internal membrane components and delivering luminal cargo to the cytoplasm. Here, we use a previously established ex vivo approach to investigate the cellular fate of EVs spiked into whole blood samples from nonhuman primate (NHP) and human donors and contrast these findings with results from in vitro assays. We report that EVs are internalized by NHP and human B cells while also associating to some degree with other PBMCs. EVs exhibit greater association with B cells in ex vivo whole blood compared to isolated B cells, suggesting that blood components may promote EV interactions or that cell isolation factors may inhibit this association. Cellular uptake of EVs involves clathrin-dependent endocytosis and may be aided by other pathways, including direct EV-cell membrane fusion. Overall, our data suggest that EV association, including uptake, by B cells occurs in at least two primate species. These findings highlight the potential to develop new strategies to either enhance or inhibit EV tropism toward B cells.