IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fcγ receptors
IgG2a-mediated enhancement of antibody and T cell responses and its relation to inhibitory and activating Fcγ receptors
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DOI：
10.4049/jimmunol.172.9.5269
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发表时间：
2004-05-01
影响因子：
4.4
通讯作者：
Heyman, B
中科院分区：
文献类型：
--
作者：
Getahun, A;Dahlström, J;Heyman, B
在实验动物模型中的许多研究指出Fc γ R在自身免疫和变态反应中的重要作用。在这项研究中，我们研究了IgG的产生，导致炎症的事件链中的早期步骤，是如何通过激活和抑制Fc γ R来调节的。已知IgG Ab反馈增强Ab对可溶性Ag的应答，并且这种作用需要激活Fc γ R。为了测试Th细胞的增殖，在用IgG 2a抗2，4，6-三硝基苯基（TNP）加OVA-TNP或单独用OVA-TNP免疫之前，用表达转基因OVA特异性TCR的CD 4（+）T细胞过继转移小鼠。IgG 2a诱导了OVA特异性T细胞数量的显著增加，这先于OVA特异性Ab应答，并且依赖于FcR γ链。在缺乏该受体的小鼠中研究了抑制性Fc γ RIIB在Ab应答中的作用。尽管IgG 2a增强了野生型小鼠的初级抗体应答、生发中心的发育和免疫记忆，但在Fc γ RIIB（-/-）小鼠中增强作用明显更强。所提供的数据与以下假设一致，即IgG 2a介导的Ab应答上调背后的机制涉及FcR γ（+）APC向CD 4（+）T细胞的Ag呈递增加。我们的观察也说明了IgG抗体的复杂的免疫调节作用。一方面，它们通过激活Fc γ R增强Ab应答，另一方面，它们通过Fc γ RIIB为相同的Ab应答设定上限。
A number of studies in experimental animal models point to an important role of FcgammaRs in autoimmunity and allergy. In this study, we investigate how the production of IgG, an early step in the chain of events leading to inflammation, is regulated by activating and inhibitory FcgammaRs. IgG Abs are known to feedback-enhance Ab responses to soluble Ags, and this effect requires activating FcgammaRs. To test proliferation of Th cells, mice were adoptively transferred with CD4(+) T cells expressing a transgenic OVA-specific TCR before immunization with IgG2a anti-2,4,6-trinitrophenyl (TNP) plus OVA-TNP or with OVA-TNP alone. IgG2a induced a significant increase in OVA-specific T cell numbers, which preceded the OVA-specific Ab response and was dependent on the FcRgamma chain. The role of the inhibitory FcgammaRIIB in Ab responses was studied in mice lacking this receptor. Although IgG2a enhanced primary Ab responses, development of germinal centers, and immunological memory in wild-type mice, enhancement was markedly stronger in FcgammaRIIB(-/-) mice. The presented data are compatible with the hypothesis that the mechanism behind IgG2a-mediated up-regulation of Ab responses involves increased Ag presentation to CD4(+) T cells by FcRgamma(+) APCs. Our observations also illustrate the intricate immunoregulatory role of IgG Abs. On the one hand, they enhance Ab responses via activating FcgammaRs, and on the other hand, they set an upper limit for the same Ab response via FcgammaRIIB.