Suppression of allergy with non-specific monoclonal IgE antibodies.

虽然巴西尼波圆线虫（Nippostrongylus brasiliensis, Nb）初次感染后会产生高水平的IgE，但大多数IgE抗体（Abs）不是针对该蠕虫的特异性抗体。Western blotting和酶联免疫吸附实验显示，来自nb感染的BALB/c小鼠的IgE抗体对蠕虫无细胞提取物中存在的nb衍生的排泄-分泌蛋白和抗原没有反应性。从感染Nb的小鼠中获得的单克隆IgE抗体也不与这些Nb抗原反应。为了表征nb诱导的IgE反应，我们使用（QM x C57BL/6）F1 （QBF1）小鼠，该小鼠携带敲入17.2.25 VHDJH片段（VHT），编码4-羟基-3-硝基苯乙酰半抗原特异性的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LPS + IL-4培养的QBF1 B细胞中，超过80%的IgE抗体携带vht编码的H链。相比之下，当QBF1小鼠感染Nb时，只有不到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。我们在小鼠实验中发现，B细胞重新表达RAG-1和RAG-2蛋白，并在外周发生Ig基因的二次重排（受体编辑）。综上所述，数据表明，nb诱导的小鼠IgE反应不仅仅是B细胞多克隆活化的结果，而且可能涉及次要修改Ig基因的机制。

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.