Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse

Makiko Suzuki, Takeshi Takahashi, Ikumi Katano, Ryoji Ito, Mamoru Ito, Hideo Harigae, Naoto Ishii, Kazuo Sugamura

Research output: Contribution to journalArticlepeer-review

60 Citations (Scopus)


Mounting evidence has demonstrated that NOD-Shi/scid/γcnull (NOG) mice are one of the most suitable mouse strains for humanized mouse technologies, in which various human cells or tissues can be engrafted without rejection and autonomously maintained. We have characterized and analyzed various features of the human immune system reconstituted in NOG mice by transplanting human hematopoietic stem cells (hu-HSC). One of the problems of the quasi-immune system in these hu-HSC NOG mice is that the quality of immune responses is not always sufficient, as demonstrated by the lack of IgG production in response to antigen challenge. In this study, we established a novel transgenic NOG sub-strain of mice bearing the HLA-DRA and HLA-DRB1:0405 genes, which specifically expresses HLA-DR4 molecules in MHC II-positive cells. This mouse strain enabled us to match the haplotype of HLA-DR between the recipient mice and human donor HSC. We demonstrated that T-cell homeostasis was differentially regulated in HLA-matched hu-HSC NOG mice compared with HLA-mismatched control mice, and antibody class switching was induced after immunization with exogenous antigens in HLA-matched mice. This novel mouse strain improves the reconstituted human immune systems that develop in humanized mice and will contribute to future studies of human humoral immune responses.

Original languageEnglish
Pages (from-to)243-252
Number of pages10
JournalInternational immunology
Issue number4
Publication statusPublished - 2012 Apr 1


  • Adaptive immunity
  • HLA-DR
  • Humanized mice
  • NOG mice
  • Transgenic

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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