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- Sun, Jia-Bin, 1948, et al.
(author)
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Important Role for Fc gamma RIIB on B Lymphocytes for Mucosal Antigen-Induced Tolerance and Foxp3(+) Regulatory T Cells
- 2013
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In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 191:8, s. 4412-4422
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Journal article (peer-reviewed)abstract
- Fc gamma RIIB, the only Fc gamma R expressed on B cells, is important in the maintenance of immunological tolerance to self-Ags. In this study, we investigated the role of Fc gamma RIIB 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 Fc gamma RIIB-expressing wild-type (WT), but not Fc gamma RIIB-/-, mice. Such mucosally induced tolerance (oral tolerance) associated with induction of Ag-specific Foxp3(+) regulatory T cells was restored in Fc gamma RIIB-/- 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 mu MT mice that received Fc gamma RIIB-overexpressing B cells before treatment. Furthermore, cell transfer in either WT or mu MT mice of WT but not Fc gamma RIIB-/- 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 Fc gamma RIIB expression on B cells, in addition to dendritic cells, is important for mucosal induction of Ag-specific immune tolerance.
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