Enhanced Antibody Responses in a Novel NOG Transgenic Mouse with Restored Lymph Node Organogenesis

Lymph nodes (LNs) are at the center of adaptive immune responses. Various exogenous substances are transported into LNs and a series of immune responses ensue after recognition by antigen-specific lymphocytes. Although humanized mice have been used to reconstitute the human immune system, most lack LNs due to deficiency of the interleukin (IL)-2R. gene (cytokine common gamma chain, gamma c). In this study, we established a transgenic strain, NOG-pROR gamma t-gamma c, in the NOD/shi-scid-IL-2R gamma(null) (NOG) background, in which the gamma c gene was expressed in a lymph-tissue inducer (LTi) lineage by the endogenous promoter of ROR gamma t. In this strain, LN organogenesis was normalized and the number of human T cells substantially increased in the periphery after reconstitution of the human immune system by human hematopoietic stem cell transplantation. The distribution of human T cells differed between NOG-pROR gamma t-gamma c Tg and NOG-non Tg mice. About 40% of human T cells resided in LNs, primarily the mesenteric LNs. The LN-complemented humanized mice exhibited antigen-specific immunoglobulin G responses together and an increased number of IL-21(+)-producing CD4(+) T cells in LNs. This novel mouse strain will facilitate recapitulation of human immune responses.