Accelerated antigen presentation and elicitation of humoral response in vivo by FcgammaRIIB- and FcgammaRI/III-mediated immune complex uptake.
Accelerated antigen presentation and elicitation of humoral response in vivo by FcgammaRIIB- and FcgammaRI/III-mediated immune complex uptake.
复制标题
通过 FcgammaRIIB 和 FcgammaRI/III 介导的免疫复合物摄取加速体内抗原呈递并引发体液反应。
作者：
A. Yada;S. Ebihara;Kimio Matsumura;Shota Endo;Tsutomu Maeda;A. Nakamura;Kenichi Akiyama;S. Aiba;T. Takai
已经确定IgG的活化型Fc受体（Fc γ R），如Fc γ RI和Fc γ RIII，对于诱导炎症反应是必需的，而独特的抑制性Fc γ R，Fc γ RIIB，在IgG-免疫复合物连接后抑制细胞内信号传导，并且可以抑制炎症和自身免疫。尽管抗原呈递是引起炎症反应的关键步骤，但Fc γ RIIB对抗原呈递的贡献在其是否正性或负性调节抗原呈递细胞（APC），特别是树突状细胞（DC）方面存在争议。在本报告中，我们表明，抗原靶向激活型Fc γ R，Fc γ RI/III，抑制性Fc γ RIIB对骨髓来源的DC和巨噬细胞和原代表皮朗格汉斯细胞增强T细胞增殖在体外，并引起体液反应后过继转移的抗原脉冲的DC。缺乏Fc γ RIIB的DC显示出IC摄取能力的降低和T细胞刺激的降低，并且诱导的IgG产生效率低于来自野生型小鼠的DC。另一方面，缺乏FcR共同γ亚基的DC（其仅表达FcgammaRIIB）与FcgammaR无效DC相比显示出IC摄取、T细胞增殖和IgG产生的显著上调，证明FcgammaRIIB对于IgG复合抗原的有效抗原呈递的正调节。这些结果支持抗原靶向APC上的Fc γ R在各种炎性病症中的治疗益处。
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.