Role of Lymphocyte Subsets in the Immune Response to Primary B Cell-Derived Exosomes

• Published in: The Journal of immunology (1950) 2017-10, Vol.199 (7), p.2225-2235
• Main Authors: Saunderson, Sarah C, McLellan, Alexander D
• Format: Article
• Language: English
• Subjects: Animals; Antigen presentation; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cross-Priming; Cytotoxicity; Cytotoxicity, Immunologic; Dendritic cells; Dendritic Cells - immunology; Depletion; Exosomes; Exosomes - immunology; Exosomes - ultrastructure; Immune response; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lymphocyte Activation; Lymphocyte receptors; Lymphocyte Subsets - classification; Lymphocyte Subsets - immunology; Lymphocyte Subsets - metabolism; Lymphocytes; Lymphocytes B; Lymphocytes T; Major histocompatibility complex; Mice; Mice, Inbred C57BL; Microscopy, Electron; Natural killer cells; Proteins; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Rodents; Spleen; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1601537

Exosomes are lipid nanovesicles released after fusion of the endosomal limiting membrane with the plasma membrane. In this study, we investigated the requirement for CD4 T cells, B cells, and NK cells to provide help for CD8 T cell-mediated response to B cell-derived exosomes. CTL responses to Ag-loaded exosomes were dependent on host MHC class I, with a critical role for splenic langerin CD8α dendritic cells (DCs) in exosomal Ag cross-presentation. In addition, there was an absolute dependence on the presence of CD4 T cells, CD8 T cells, and NK cells, where the loss of any one of these subsets led to a complete loss of CTL response. Interestingly, NK cell depletion experiments demonstrated a critical cutoff point for depletion efficacy, with low-level residual NK cells providing sufficient help to allow optimal CD8 T cell proliferative responses to exosomal protein. Despite the potential role for B cells in the response to B cell-derived exosomal proteins, B cell depletion did not alter the exosome-induced CTL response. Similarly, a possible role for the BCR or circulating Ab in mediating CTL responses to B cell-derived exosomes was ruled out using D LMP2A mice, which lack secreted and membrane-bound Ab, yet harbor marginal zone and follicular B cells. In contrast, CTL responses to DC-derived exosomes were significantly inhibited within Ab-deficient D LMP2A mice compared with wild-type mice. However, this response was not restored upon serum transfer, implicating a role for the BCR, but not circulating Ab, in DC-derived exosome responses.