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

First Author  Saunderson SC Year  2017
Journal  J Immunol Volume  199
Issue  7 Pages  2225-2235
PubMed ID  28842467 Mgi Jnum  J:256381
Mgi Id  MGI:6103416 Doi  10.4049/jimmunol.1601537
Citation  Saunderson SC, et al. (2017) Role of Lymphocyte Subsets in the Immune Response to Primary B Cell-Derived Exosomes. J Immunol 199(7):2225-2235
abstractText  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(+) CD8alpha(+) 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 DHLMP2A 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 DHLMP2A 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.
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