Exosomes are the membrane pockets that lie within larger vesicles called multivesicular bodies (MVBs). In B cells and other antigen-presenting cells, MVBs and exosomes house antigens in complex with the MHC class II molecules that present them to T cells. When an MVB fuses with the plasma membrane, MHC-antigen from the MVB membrane is displayed on the B cell surface, while the exosome allotment of MHC-antigen is sent out into the extracellular environment.
In the new study, the authors found that a B cell shot out twice as many exosomes when it met a T cell that recognized its antigen. In turn, the exosomes stimulated the T cells to divide rapidly and make cytokines that further activate B cells.
The resulting T cell progeny also need to see antigen to be activated. Roche wondered, “How are those daughters getting stimulated from one lone B cell?” He imagines that the exosome secretion speeds the process.
“We think of it like a shotgun blast,” says Roche. “The T cell tells the B cell to shoot out its exosomes, and they help activate the new T cells.” Testing the theory will be difficult, however. “No one knows what exosomes do in real life; we have not been able to stop a cell from secreting them without killing it.”
The signal to release exosomes seems to stem from the MHC molecule, probably upon binding to the T cell receptor. Artificially cross-linking MHC molecules also stimulated the release. Downstream tyrosine kinases were also required, but more signaling details are so far unavailable.
Exosomes acquired their MHC-antigen pairs via recycling from the cell surface. Perhaps sending out the exosomes saves recycled MHC-antigen from its alternative fate—lysosomal degradation. After all, once an enemy is found, MHC weapons are in high demand.