HIV-mediated expression of Btk in hematopoietic stem cells is not sufficient to restore B cell function in X-linked immunodeficient mice.
Mutations of Bruton's tyrosine kinase (Btk), which is critical for B cell development and function, cause X-linked agammaglobulinemia (XLA) in humans and X-linked immunodeficiency (xid) in mice. Although the severity of the clinical phenotype differs between the two species, xid mice are considered useful for evaluating treatment strategies for XLA patients. Hematopoietic stem cells (HSCs; 1 approximately 3 x 10(5))from xid mice were transduced with an HIV vector containing the human Btk (hBtk) gene under the control of the internal murine stem cell virus (MSCV) promoter and injected into 4-week-old xid mice. Thirty weeks later, the copy number of the integrated HIV vector was over 0.2 per cell in both bone marrow and spleen, but serum concentrations of IgM and IgG3 and the antibody response to nitrophenol (NP)-Ficoll challenge were not restored. The number of differentiated B cells (IgM(low)IgD(high)) was increased, while the peritoneal B1 cell count remained low. These results indicate that HIV-mediated expression of hBtk in bone marrow stem cells partially promotes B cell development, but is not sufficient for the restoration of B cell function in xid mice.
Tanabe
Hiroko
H
Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo, Japan.
Miyake
Koichi
K
Shimada
Takashi
T
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D051379:Mice; D016513:Mice, SCID; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D016511:Severe Combined Immunodeficiency / Q000201:enzymology*
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse