Normal and Pathological Development of Human B Cells in HumanizedMice Transplanted with Normal and XLA patients

Research Project

Project/Area Number	22790986
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Pediatrics
Research Institution	Kyushu University
Principal Investigator	DOI Takehiko 九州大学, 大学病院, 特任講師 (20572100)
Project Period (FY)	2010 – 2012
Project Status	Completed (Fiscal Year 2012)
Budget Amount *help	¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000) Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	ヒト化マウス / B細胞 / 原発性免疫不全症候 / 原発性免疫不全症候群 / 原発性免不全症候群
Research Abstract	X-linked agammaglobulinemia (XLA) is a primary B cell deficiency and hypogammaglobulinemia due to the absence of the BTKgene. In this study, we generated human XLA mouse model using NOD/SCID/IL2rγnull mouse. The recipients engrafted with XLA patient human stem cells (HSCs) demonstrated significant pathology in human B cell development in vivo, including severe B cell maturation arrest and impaired immunoglobulin production, in contrast with the mice22790986seika engrafted with normal human HSCs. These in vivomodels of human hematopoiesis enable direct in vivo investigation of normal and pathological human B cell ontogeny and facilitate the development of therapeutic strategies