Follicular dendritic cell (FDC)-FcγRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development
Follicular dendritic cell (FDC)-FcγRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development
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DOI：
10.1002/eji.200636122
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Tew, John G.
中科院分区：
文献类型：
--
作者：
El Shikh, Mohey Eldin;El Sayed, Rania;Tew, John G.
在用Ag主动免疫的小鼠攻击后1-3天，滤泡树突状细胞（FDC）-Fc γ RIIB水平上调。这种动力学表明，记忆细胞并不驱动这种反应，从而提出了免疫复合物（IC）-FDC相互作用导致FDC活化的假设。为了测试这一点，用抗-OVA Ab被动免疫的小鼠被OVA攻击以产生IC。3天后，分析FDC上IC、Fc γ RIIB、ICAM-1和VCAM-1的水平。还在体外用IC刺激FDC，并通过定量RT-PCR定量Fc γ RIIB、ICAM-1和VCAM-1的mRNA。在被动免疫的WT和Fc γ RIIB-/-小鼠中的IC标记显示每个LN正中矢状切片有5至6个FDC-网状结构。在WT小鼠中，这些携带IC的FDC-网状物与Fc γ R11 B、ICAM-1和VCAM-1的FDC-网状物标记相对应。通过流式细胞术证实了IC刺激的FDC上这些分子的增加。与此形成鲜明对比的是，在Fc γ RIIB-/-小鼠中，在携带IC的FDC-网状物上或在纯化的FDC上未观察到VCAM-1或ICAM-1增加。在体外添加IC导致WT FDC中Fc γ RIIB、ICAM-1和VCAM-1的mRNA显著增加，但在来自Fc γ RIIB-/-小鼠的FDC、2.4 G2预处理的WT FDC、B细胞或巨噬细胞中未导致显著增加。因此，尽管FDC-Fc γ RIIB对于IC捕获不是必需的，但FDC-Fc γ RIIB与IC的接合启动了FDC活化途径。
Follicular dendritic cell (FDC)-Fc gamma RIIB levels are up-regulated 1-3 days after challenge of actively immunized mice with Ag. This kinetics suggested that memory cells are not driving this response, prompting the hypothesis that immune complex (IC)-FDC interactions lead to FDC activation. To test this, mice passively immunized with anti-OVA Ab were OVA challenged to produce IC. After 3 days, levels of IC, Fc gamma RIIB, ICAM-1, and VCAM-1 on FDC were analyzed. FDC were also stimulated with IC in vitro, and mRNA for Fc gamma RIIB, ICAM-1, and VCAM-1 was quantified by quantitative RT-PCR. IC labeling in passively immunized WT and Fc gamma RIIB-/- mice revealed five to six FDC-reticula per LN midsagittal section. In WT mice, these IC-bearing FDC-reticula corresponded with FDC-reticula labeling for Fc gamma R11B, ICAM-1, and VCAM-1. Increases in these molecules on IC-stimulated FDC were confirmed by flow cytometry. In marked contrast, in Fc gamma RIIB-/- mice, no increased VCAM-1 or ICAM-1 was seen on IC-bearing FDC-reticula or on purified FDC. Addition of IC in vitro resulted in dramatic increases in mRNA for Fc gamma RIIB, ICAM-1 and VCAM-1 in WT FDC, but not in FDC from Fc gamma RIIB-/- mice, 2.4G2-pretreated WT FDC, B cells, or macrophages. Thus, although FDC-Fc gamma RIIB was not essential for IC trapping, engagement of FDC-Fc gamma RIIB with IC initiated an FDC activation pathway.