title: Important role for FcγRIIB on B lymphocytes for mucosal antigen-induced tolerance and Foxp3+ regulatory T cells.
abstract: FcγRIIB, the only FcγR expressed on B cells, is important in the maintenance of immunological tolerance to self-Ags. In this study, we investigated the role of FcγRIIB in Ag-specific CD4 T cell tolerance induced by mucosally administered Ag (OVA) coupled to cholera toxin B subunit (Ag/CTB) or given alone. We found that sublingual administration of Ag/CTB conjugate or intragastric administration of a >100-fold higher dose of Ag alone efficiently suppressed parenteral immunization-induced Ag-specific T cell proliferation and delayed-type hypersensitivity responses in FcγRIIB-expressing wild-type (WT), but not FcγRIIB(-/-), mice. Such mucosally induced tolerance (oral tolerance) associated with induction of Ag-specific Foxp3(+) regulatory T cells was restored in FcγRIIB(-/-) mice by adoptive transfer of either WT B cells or WT dendritic cells before the mucosal Ag/CTB treatment; it was even more pronounced in μMT mice that received FcγRIIB-overexpressing B cells before treatment. Furthermore, cell transfer in either WT or μMT mice of WT but not FcγRIIB(-/-) B cells pretreated for 1 h in vitro with Ag/CTB conjugate induced Ag-specific immunological tolerance, which was further enhanced by adoptive transfer of WT B cells pretreated with anti-Ag IgG immune complexed Ag/CTB. We conclude that FcγRIIB expression on B cells, in addition to dendritic cells, is important for mucosal induction of Ag-specific immune tolerance.
authors.affiliation: University of Gothenburg Vaccine Institute, SE405 30 Göteborg, Sweden;
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Sun
authors.forename: Zou
authors.initials: Z
authors.lastname: Xiang
authors.forename: Kenneth G C
authors.initials: KG
authors.lastname: Smith
authors.forename: Jan
authors.initials: J
authors.lastname: Holmgren
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D001324:Autoantigens; C499172:Fcgr2b protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D017452:Receptors, IgG; D010047:Ovalbumin; D002772:Cholera Toxin