T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes

Antigen‐specific interactions between B cells and T cells are essential for the generation of an efficient immune response. Since this requires peptide–MHC class II complexes (pMHC‐II) on the B cell to interact with TCR on antigen‐specific T cells, we have examined the mechanisms regulating the persistence, loss, and secretion of specific pMHC‐II complexes on activated B cells. Using a mAb that recognizes specific pMHC‐II, we found that activated B cells degrade approximately 50% of pMHC‐II every day and release 12% of these pMHC‐II from the cell on small membrane vesicles termed exosomes. These exosomes directly stimulate primed, but not naïve, CD4 T cells. Interestingly, engagement of antigen‐loaded B cells with specific CD4 T cells stimulates exosome release in a manner that can be mimicked by pMHC‐II crosslinking. Biochemical studies revealed that the pMHC‐II released on exosomes was previously expressed on the plasma membrane of the B cells, suggesting that regulated exosome release from activated B cells is a mechanism to allow pMHC‐II to escape intracellular degradation and decorate secondary lymphoid organs with membrane‐associated pMHC‐II complexes.