Involvement of insulin-like growth factor-I and insulin-like growth factor binding proteins in pro-B-cell development.
OBJECTIVE
Insulin-like growth factor (IGF)-binding proteins (IGFBPs) are a family of proteins thought to modulate IGF function. By employing an in vitro culture system of human hematopoietic stem cells cocultured with murine bone marrow stromal cells, we examined the effects of IGF-I and IGFBPs on early B-cell development.


METHODS
Human CD34(+) bone marrow cells were cocultured with murine stromal MS-5 cells for 4 weeks, and pro-B-cell number was analyzed by flow cytometry. After administration of reagents that are supposed to modulate IGF-I or IGFBP function to the culture, the effect on pro-B-cell development was examined.


RESULTS
After cultivation for 4 weeks, effective induction of pro-B-cell proliferation was observed. Experiments using several distinct factors, all of which neutralize IGF-I function, revealed that impairment of IGF-I function results in a significant reduction in pro-B-cell development from CD34(+) cells. In addition, when the effect of recombinant proteins of IGFBPs and antibodies against IGFBPs were tested, IGFBP-3 was found to inhibit pro-B-cell development, while IGFBP-6 was required for pro-B-cell development.


CONCLUSIONS
IGF-I is essential for development of bone marrow CD34(+) cells into pro-B cells. Moreover, IGFBPs are likely involved in regulation of pro-B-cell development.
Department of Developmental Biology, National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan. ttaguchi@nch.go.jp
Tomoko
T
Taguchi
Hisami
H
Takenouchi
Jun
J
Matsui
Wei-Ran
WR
Tang
Mitsuko
M
Itagaki
Yusuke
Y
Shiozawa
Kyoko
K
Suzuki
Sachi
S
Sakaguchi
Yohko U
YU
Ktagiri
Takao
T
Takahashi
Hajime
H
Okita
Junichiro
J
Fujimoto
Nobutaka
N
Kiyokawa
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018920:Coculture Techniques; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology
D018952:Antigens, CD34; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I