Human Adaptive Immune System Rag2−/−γc−/− Mice

: Although many biologic principles are conserved in mice and humans, species‐specific differences exist, for example, in susceptibility and response to pathogens, that often do not allow direct implementation of findings in experimental mice to humans. Research in humans, however, for ethical and practical reasons, is largely restricted to in vitro assays that lack components and the complexity of a living organism. To nevertheless study the human hematopoietic and immune system in vivo, xenotransplantation assays have been developed that substitute human components to small animals. Here, we summarize our recent findings that transplantation of human cord blood CD34+ cells to newborn Rag2−/−γc−/− mice leads to de novo development of major functional components of the human adaptive immune system. These human adaptive immune system Rag2−/−γc−/− (huAIS‐RG) mice can now be used as a technically straightforward preclinical model to evaluate in vivo human adaptive immune system development as well as immune responses, for example, to vaccines or live infectious pathogens.