Accelerated antigen presentation and elicitation of humoral response in vivo by FcγRIIB- and FcγRI/III-mediated immune complex uptake

Ayumi Yada, Shin Ebihara, Kimio Matsumura, Shota Endo, Tsutomu Maeda, Akira Nakamura, Kenichi Akiyama, Setsuya Aiba, Toshiyuki Takai

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

It is well established that activating-type Fc receptors for IgG (FcγR), such as FcγRI and FcγRIII, are essential for inducing inflammatory responses, whereas a unique inhibitory FcγR, FcγRIIB, 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 FcγRIIB 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 FcγRs, FcγRI/III, and inhibitory FcγRIIB 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 FcγRIIB 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 γ subunit, which only expresses FcγRIIB, showed significant up-regulations of IC-uptake, T-cell proliferation, and IgG production compared to those of FcγR null DC, demonstrating a positive regulation of FcγRIIB for the efficient antigen presentation of IgG-complexed antigens. These results support the therapeutic benefits of antigen-targeting to FcγR on APC in the various inflammatory disorders.

Original languageEnglish
Pages (from-to)21-32
Number of pages12
JournalCellular Immunology
Volume225
Issue number1
DOIs
Publication statusPublished - 2003 Jan 1

Keywords

  • Antigen presentation
  • Dendritic cell
  • Fc receptor
  • Humoral response
  • Vaccination

ASJC Scopus subject areas

  • Immunology

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