Development of humanized mouse with functional immune systems

通过移植人造血干细胞在严重免疫缺陷的NOG小鼠中重建人造血和免疫系统的人源化小鼠受到了很多关注。在人源化小鼠中，针对外源性物质的体液免疫应答通常较弱。特别是，IgG反应很难诱导。为了改善免疫系统，我们建立了一种新的小鼠品系，表达人类HLA II类基因。我们发现HLA-DR 4表达的NOG小鼠在移植来自HLA单倍型相同供体的HSC时，可产生抗原特异性的人IgG应答。 该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.