title: Simultaneous presentation and cross-presentation of immune-stimulating complex-associated cognate antigen by antigen-specific B cells.
abstract: We demonstrate that uptake of oligomeric cognate antigen (OVA-hen egg lysozyme, OVA-HEL) alone or incorporated in immune-stimulating complexes (ISCOMS) facilitates presentation and simultaneous cross-presentation of OVA by HEL-specific B cells in vitro. HEL-specific B cells stimulated CD8(+) T cell responses in vitro to the same extent as bone marrow-derived dendritic cells. Cross-presentation by specific B cells required endosomal acidification, proteasomal processing and classical MHC class I/peptide transport. Specific B cells also acquired both antigens rapidly in vivo and presented them to CD4(+) T cells. However, only HEL-specific B cells from OVA-HEL ISCOMS-immunised mice could cross-present OVA to naive OVA-specific CD8(+) T cells. Antigen-specific B cells were also activated selectively by OVA-HEL ISCOMS in vitro and importantly, the presence of HEL-specific B cells promoted the persistence of clonal expansion of OVA-specific CD8(+) T cells after in vivo immunisation with OVA-HEL ISCOMS. These results demonstrate preferential MHC class I and class II processing of cognate antigen incorporated in ISCOMS by specific B cells in vitro and in vivo, highlighting the ability of ISCOMS to target B cells and offering novel insights into the role of B cells in cross-presentation to CD8(+) T cells.
authors.affiliation: Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Robson
authors.forename: Anne M
authors.initials: AM
authors.lastname: Donachie
authors.forename: Allan McI
authors.initials: AM
authors.lastname: Mowat
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D020126:Brefeldin A / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D049109:Cell Proliferation; D002738:Chloroquine / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D016882:ISCOMs; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009113:Muramidase / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014611:Vaccination
chemical_list: D000941:Antigens; D015853:Cysteine Proteinase Inhibitors; D018985:Epitopes, B-Lymphocyte; D016882:ISCOMs; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C067713:lactacystin; D020126:Brefeldin A; D002738:Chloroquine; D010047:Ovalbumin; C421864:hen egg lysozyme; D009113:Muramidase; D000111:Acetylcysteine