B cell extracellular vesicles contain monomeric IgM that binds antigen and enters target cells

The production and release of small phospholipid membrane vesicles, or extracel-lular vesicles (EVs), is a trait of most prokaryotic and eukaryotic cells. EVs display heterogeneity in content, size, biogenesis, activity, and function. B cells uniquely express immunoglobulin and produce EVs; however, the relationship between these entities has not been clarified. Here, we used several methodologies to isolate large (11,000 3 g) and small (110,000 3 g) EVs and evaluate their IgM con-tent, characteristics and activity. We found that B cells from multiple cell lines and primary B cells produce EVs that display monomeric IgM on the surface and contain encapsulated monomeric IgM, which is independent of secreted pen-tameric IgM. Our data indicate EV IgM can bind antigen specifically, and EV IgM can be incorporated intracellularly into secondary cells. These results sug-gest immunological activities different from secreted pentameric IgM that may constitute a separate and distinct antibody distribution system.