| Title | Accelerated antigen presentation and elicitation of humoral response in vivo by FcgammaRIIB- and FcgammaRI/III-mediated immune complex uptake. | | Author(s) | Yada A, Ebihara S, Matsumura K, Endo S, Maeda T, Nakamura A, Akiyama K, Aiba S, Takai T | | Institution | Department of Experimental Immunology and the CREST Program of Japan Science and Technology Corporation, Institute of Development, Aging and Cancer, Tohoku University, 980-8575, Sendai, Japan. | | Source | Cell Immunol 2003 Sep; 225(1):21-32. | | MeSH | Animals
Antigen Presentation
Antigen-Antibody Complex
Antigens, CD
Cell Division
Dendritic Cells
Female
Flow Cytometry
Gene Expression Regulation
Immunoglobulin G
Immunohistochemistry
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovalbumin
Receptors, IgG
Research Support, Non-U.S. Gov't
Spleen
T-Lymphocytes
| | Abstract | It is well established that activating-type Fc receptors for IgG (FcgammaR), such as FcgammaRI and FcgammaRIII, are essential for inducing inflammatory responses, whereas a unique inhibitory FcgammaR, FcgammaRIIB, inhibits intracellular signaling upon ligation of IgG-immune complexes, and can suppress inflammation and autoimmunity. Although antigen presentation is a crucial step for evoking inflammatory responses, the contribution of FcgammaRIIB to antigen presentation is controversial as to whether it regulates antigen-presenting cells (APC), particularly dendritic cells (DC), positively or negatively. In the present report, we show that the antigen targeting to both activating-type FcgammaRs, FcgammaRI/III, and inhibitory FcgammaRIIB on bone marrow-derived DC and macrophages and primary epidermal Langerhans' cells augmented T cell proliferation in vitro and elicited humoral responses upon adoptive transfer of the antigen-pulsed DC. The DC lacking FcgammaRIIB showed a reduction in IC-uptake ability and a decreased T-cell stimulation, and induced less efficient IgG production than those of DC from wild-type mice. On the other hand, the DC lacking FcR common gamma subunit, which only expresses FcgammaRIIB, showed significant up-regulations of IC-uptake, T-cell proliferation, and IgG production compared to those of FcgammaR null DC, demonstrating a positive regulation of FcgammaRIIB for the efficient antigen presentation of IgG-complexed antigens. These results support the therapeutic benefits of antigen-targeting to FcgammaR on APC in the various inflammatory disorders. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 14643301 |
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