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

The production and release of small phospholipid membrane vesicles, or extracellular 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 × g) and small (110,000 × g) EVs and evaluate their IgM content, 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 pentameric IgM. Our data indicate EV IgM can bind antigen specifically, and EV IgM can be incorporated intracellularly into secondary cells. These results suggest immunological activities different from secreted pentameric IgM that may constitute a separate and distinct antibody distribution system.