Development of novel humanized NOG mice producing human IgG antibody

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The purpose in this research is to produce human IgG antibody using humanized NOG mice that were reconstituted with the human immune system. In this study, we attempted to develop five strains of transgenic (Tg) NOG mice carrying human genes (hIL-7, hLymphotoxin, hCXCL13, hIL-6 and hIFNγ), which are important for the development and functional maturation of immune cells. We confirmed the expression of transgenes, hIL-7, hLymphotoxin and hIL-6 in three strains of Tg mice. Hematopoietic stem cell transplantation into hLymphotoxin Tg mice and substitution of the genetic background of hIL-6 Tg mice in NOG mice are currently underway. We report here that the results obtained by hIL-7 Tg NOG mice reconstituted with the human immune system. We analyzed engraftment and differentiation of human T and B cells in hIL-7 Tg mice by flow cytometry. As a result, the engraftment rate of human cells and differentiation into T and B cells did not differ between hIL-7 Tg NOG and control non-Tg NOG mice. To determine the potential of cell growth of human T cells developed in hIL-7 Tg NOG mice, we isolated human T cells from the spleen and stimulated them with anti-human CD3 and CD28 antibodies in vitro. As a result, human T cells from hIL-7 Tg NOG mice showed significantly higher proliferation than those from non-Tg NOG mice. This result suggests that IL-7 signaling can induce the growth phase, in differentiated human T cells, which presumably become capable of rapid elimination of foreign pathogens. Therefore, hIL-7 Tg NOG mice have potential as a useful tool in the form of humanized mice reconstituted with the human immune system. We are attempting to produce human IgG antibodies by immunization of T cell dependent antigens using hIL-7 Tg NOG mice.