Accelerated antigen presentation and elicitation of humoral response in vivo by FcgammaRIIB- and FcgammaRI/III-mediated immune complex uptake.
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.
Yada
Ayumi
A
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.
Ebihara
Shin
S
Matsumura
Kimio
K
Endo
Shota
S
Maeda
Tsutomu
T
Nakamura
Akira
A
Akiyama
Kenichi
K
Aiba
Setsuya
S
Takai
Toshiyuki
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C080571:Fc gamma receptor IIB; D007074:Immunoglobulin G; D017452:Receptors, IgG; D010047:Ovalbumin