Development of humanized mouse with functional immune systems

在严重免疫缺陷的NOG小鼠中，通过移植人造血干细胞来重建人的造血和免疫系统的人源化小鼠受到了极大的关注。在人源化小鼠中，对外源性物质的体液免疫反应一般较弱。尤其是，免疫球蛋白反应很难诱导。为了改善免疫系统，我们建立了一种新的表达人类HLAII类基因的小鼠品系。我们发现表达人类白细胞抗原-DR4的NOG小鼠与来自人类白细胞抗原单倍型相合的供者的造血干细胞移植后，能够产生抗原特异性的人免疫球蛋白G反应。这一模型将有助于研究人类免疫反应和开发各种治疗药物。

Humanized mice, in which human hematopoietic and immune systems are reconstituted in severe immunodeficient NOG mice by transplanting human hematopoietic stem cells, have a lot of attention. In the humanized mouse, humoral immune responses against exogenous substances are generally weak. IgG responses, especially, have been difficult to induce. To improve the immune systems, we established a novel mouse strain which expresses human HLA class II genes. We found that the HLA-DR4 expressing NOG mice could produce antigen specific human IgG responses, when they were transplanted with HSC from HLA-haplotype identical donors. This model will be useful to study human immune responses and in developing various therapeutic drugs.