First Author | Sun JB | Year | 2013 |
Journal | J Immunol | Volume | 191 |
Issue | 8 | Pages | 4412-22 |
PubMed ID | 24038083 | Mgi Jnum | J:206278 |
Mgi Id | MGI:5548293 | Doi | 10.4049/jimmunol.1301324 |
Citation | Sun JB, et al. (2013) Important role for FcgammaRIIB on B lymphocytes for mucosal antigen-induced tolerance and Foxp3+ regulatory T cells. J Immunol 191(8):4412-22 |
abstractText | FcgammaRIIB, the only FcgammaR expressed on B cells, is important in the maintenance of immunological tolerance to self-Ags. In this study, we investigated the role of FcgammaRIIB 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 FcgammaRIIB-expressing wild-type (WT), but not FcgammaRIIB(-/-), mice. Such mucosally induced tolerance (oral tolerance) associated with induction of Ag-specific Foxp3(+) regulatory T cells was restored in FcgammaRIIB(-/-) 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 muMT mice that received FcgammaRIIB-overexpressing B cells before treatment. Furthermore, cell transfer in either WT or muMT mice of WT but not FcgammaRIIB(-/-) 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 FcgammaRIIB expression on B cells, in addition to dendritic cells, is important for mucosal induction of Ag-specific immune tolerance. |