Suppression of allergy with non-specific monoclonal IgE antibodies.

使用非特异性单克隆 IgE 抗体抑制过敏。

• 批准号: 10555290
• 负责人: OHMORI Hitoshi
• 金额: $ 7.55万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10555290/
• 关键词: Allergy; IgE antibody; hybridoma; monoclonal antibody; RAG genes; V(D)J recombination; nematode; transgenic mouse

Although a high level of IgE is produced after primary infection with Nippostrongylus brasiliensis (Nb), most of the IgE antibodies (Abs) are not specific to the worm. Analyses with Western blotting and enzyme-linked immunosorbent assay revealed that the IgE Abs from Nb-infected BALB/c mice did not show reactivity with Nb-derived excretory-secretory proteins and antigens present in the cell-free extracts of the worm. Monoclonal IgE Abs obtained from the Nb-infected mice were not reactive with these Nb antigen either. To characterize Nb-induced IgE response, we used (QM x C57BL/6)F1 (QBF1) mice that bear the knock-in 17.2.25 VHDJH segment (VHT) encoding a VH region specific to 4-hydroxy-3-nitrophenylacetyl hapten, and express VHT-encoded antigen receptors on 80-85% of their B cells. Consistent with the frequency of VHT-positive B cells, more than 80% of IgE Abs induced in QBF1 B cells that were cultured with LPS plus IL-4 were found to bear VHT-encoded H chains. In contrast, when QBF1 mice were infected with Nb, less than 10% of Nb-induced IgE Abs were found to use VHT.The QBF1-derived IgE did not react with Nb antigens either. We have shown in mice that B cells reexpress RAG-1 and RAG-2 proteins, and undergo secondary rearrangement of Ig genes (receptor editing) in the periphery. Taken together, data suggest that Nb-induced IgE response in mice is not merely the result of polyclonal activation of B cells, but may involve a mechanism that revise Ig genes secondarily.

尽管巴西圆线虫 (Nb) 初次感染后会产生高水平的 IgE，但大多数 IgE 抗体 (Ab) 并不是该蠕虫所特有的。蛋白质印迹和酶联免疫吸附测定分析表明，来自 Nb 感染的 BALB/c 小鼠的 IgE Ab 没有显示出与蠕虫无细胞提取物中存在的 Nb 源性排泄蛋白和抗原的反应性。从 Nb 感染小鼠获得的单克隆 IgE Ab 也不与这些 Nb 抗原发生反应。为了表征 Nb 诱导的 IgE 反应，我们使用了 (QM x C57BL/6)F1 (QBF1) 小鼠，该小鼠携带敲入 17.2.25 VHDJH 片段 (VHT)，编码对 4-羟基-3-硝基苯乙酰基半抗原具有特异性的 VH 区域，并在 80-85% 的 B 细胞上表达 VHT 编码的抗原受体。与 VHT 阳性 B 细胞的频率一致，在用 LPS 加 IL-4 培养的 QBF1 B 细胞中诱导的 IgE Ab 中，超过 80% 被发现带有 VHT 编码的 H 链。相比之下，当QBF1小鼠感染Nb时，发现不到10%的Nb诱导的IgE抗体使用VHT。QBF1衍生的IgE也不与Nb抗原发生反应。我们在小鼠中证明，B 细胞重新表达 RAG-1 和 RAG-2 蛋白，并在外周进行 Ig 基因的二次重排（受体编辑）。综上所述，数据表明，铌诱导的小鼠 IgE 反应不仅仅是 B 细胞多克隆激活的结果，而且可能涉及二次修改 Ig 基因的机制。

项目成果

Masaki Hikida: "Rerrangement of λ light chain genes in mature B cells in vitro and in vivo. Function of reexpressed recombination-activating gene (RAG) products."Journal of Experimental Medicine. Vol.187. 795-799 (1998)

Masaki Hikida：“成熟 B 细胞中 λ 轻链基因的体外和体内重排。重新表达的重组激活基因 (RAG) 产物的功能。”实验医学杂志第 795-799 卷（1998 年）。

Hitoshi ohmori: "Biological role of receptor editing in germina center B cells"Molecular Medicine. Vol.36. 20-28 (1999)

Hitoshi ohmori：“受体编辑在生殖中心 B 细胞中的生物学作用”分子医学。

Hitoshi Ohmori: "Expression and function of recombination activating genes in mature B cells."Critical Reviews in Immunology. 18. 221-235 (1998)

Hitoshi Ohmori：“成熟 B 细胞中重组激活基因的表达和功能。”免疫学批判评论。

Masaki Hikida: "Expression of recombination activating genes in germinal center B cells : involvement of interleukin 7 (IL-7) and the IL-7 receptor."Journal of Experimental Medicine. Vol.188. 365-372 (1998)

Masaki Hikida：“重组激活基因在生发中心 B 细胞中的表达：白细胞介素 7 (IL-7) 和 IL-7 受体的参与。”实验医学杂志。

Hitoshi Ohmori: "Selective augmenting effects of nitric oxide on antigen specific IgE responsein mice."Immunopharmacology. 46. 55-63 (2000)

Hitoshi Ohmori：“一氧化氮对小鼠抗原特异性 IgE 反应的选择性增强作用。”免疫药理学。