| RRC ID |
19297
|
| 著者 |
Suzuki M, Takahashi T, Katano I, Ito R, Ito M, Harigae H, Ishii N, Sugamura K.
|
| タイトル |
Induction of human humoral immune responses in a novel HLA-DR-expressing transgenic NOD/Shi-scid/γcnull mouse.
|
| ジャーナル |
Int Immunol
|
| 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.
|
| 巻・号 |
24(4)
|
| ページ |
243-52
|
| 公開日 |
2012-4-1
|
| DOI |
10.1093/intimm/dxs045
|
| PII |
dxs045
|
| PMID |
22402880
|
| MeSH |
Animals
Antigens, CD34 / analysis
Cells, Cultured
Female
HLA-DR4 Antigen / genetics
HLA-DR4 Antigen / immunology*
HLA-DRB1 Chains / genetics
HLA-DRB1 Chains / immunology*
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells / immunology*
Hematopoietic Stem Cells / metabolism
Humans
Immunity, Humoral*
Immunoglobulin Class Switching
Lymphocyte Activation
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
T-Lymphocytes / immunology*
T-Lymphocytes / metabolism
Transplantation, Heterologous
|
| IF |
3.519
|
| 引用数 |
50
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| 研究用ヒト臍帯血幹細胞 |
臍帯血 |
