title: Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse.
abstract: Mounting evidence has demonstrated that NOD-Shi/scid/γc(null) (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.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-cho, Aoba-ku, Sendai 980-8575, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Ikumi
authors.initials: I
authors.lastname: Katano
authors.forename: Ryoji
authors.initials: R
authors.lastname: Ito
authors.forename: Mamoru
authors.initials: M
authors.lastname: Ito
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D015804:HLA-DR4 Antigen / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D017578:Immunoglobulin Class Switching; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D018952:Antigens, CD34; D015804:HLA-DR4 Antigen; D059811:HLA-DRB1 Chains