B lymphocytes secrete antigen-presenting vesicles called exosomes, which contain MHC class II molecules. These exosomes are released when the limiting membrane of MIICs (major histocompatibility complex class II-enriched compartments) fuses with the plasma membrane. Exosomes were isolated from cell culture media and showed distinct surface protein composition compared to the plasma membrane. Exosome-bound MHC class II was in a compact, peptide-bound conformation, and newly synthesized MHC class II molecules were released into the extracellular medium with slow kinetics, indicating that direct fusion of MIICs with the plasma membrane is not the major pathway for MHC class II transport to the plasma membrane. Exosomes derived from both human and murine B lymphocytes induced antigen-specific MHC class II-restricted T cell responses, suggesting a role for exosomes in antigen presentation in vivo. Helper T lymphocytes recognize exogenous antigens bound to MHC class II molecules, displayed on the surface of various antigen-presenting cells (APCs) such as macrophages, B lymphocytes, and dendritic cells. MHC class II molecules are heterodimers of α and β subunits, which assemble in the endoplasmic reticulum and are transported to the Golgi complex, where they are targeted to endocytic compartments. In B cells and Langerhans cells, most intracellular class II molecules reside in MIICs, which have lysosomal characteristics and contain MHC class II molecules. MIICs are involved in antigen processing and peptide binding to class II molecules, but their functional subclasses remain to be determined. The study shows that MIICs in B cells are exocytic compartments, and exosomes released from MIICs contain MHC class II molecules and can present antigenic peptides to T cells. Exosomes may serve as a means of antigen presentation in vivo, potentially functioning as transport vehicles for MHC class II-peptide complexes. The findings suggest that exosomes play a role in antigen presentation and may contribute to the maintenance of long-term T cell memory or tolerance.B lymphocytes secrete antigen-presenting vesicles called exosomes, which contain MHC class II molecules. These exosomes are released when the limiting membrane of MIICs (major histocompatibility complex class II-enriched compartments) fuses with the plasma membrane. Exosomes were isolated from cell culture media and showed distinct surface protein composition compared to the plasma membrane. Exosome-bound MHC class II was in a compact, peptide-bound conformation, and newly synthesized MHC class II molecules were released into the extracellular medium with slow kinetics, indicating that direct fusion of MIICs with the plasma membrane is not the major pathway for MHC class II transport to the plasma membrane. Exosomes derived from both human and murine B lymphocytes induced antigen-specific MHC class II-restricted T cell responses, suggesting a role for exosomes in antigen presentation in vivo. Helper T lymphocytes recognize exogenous antigens bound to MHC class II molecules, displayed on the surface of various antigen-presenting cells (APCs) such as macrophages, B lymphocytes, and dendritic cells. MHC class II molecules are heterodimers of α and β subunits, which assemble in the endoplasmic reticulum and are transported to the Golgi complex, where they are targeted to endocytic compartments. In B cells and Langerhans cells, most intracellular class II molecules reside in MIICs, which have lysosomal characteristics and contain MHC class II molecules. MIICs are involved in antigen processing and peptide binding to class II molecules, but their functional subclasses remain to be determined. The study shows that MIICs in B cells are exocytic compartments, and exosomes released from MIICs contain MHC class II molecules and can present antigenic peptides to T cells. Exosomes may serve as a means of antigen presentation in vivo, potentially functioning as transport vehicles for MHC class II-peptide complexes. The findings suggest that exosomes play a role in antigen presentation and may contribute to the maintenance of long-term T cell memory or tolerance.