|
|
 Previous Article | Table of Contents | Next Article 
The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal-
cell-independent expansion and differentiation of human fetal pro-B cells
in vitro
R Namikawa, MO Muench, JE de Vries and MG Roncarolo
Human Immunology Department, DNAX Research Institute of Molecular and
Cellular Biology, Inc, Palo Alto, CA, USA.
The effects of a novel cytokine FLK2/FLT3 ligand (FL) on human fetal bone
marrow-derived CD34+CD19+ pro-B cells were analyzed in a stromal-
cell-independent, serum-deprived culture system. FL, like interleukin-3
(IL-3), synergized with IL-7 in promoting pro-B cell growth, and
differentiation of these cells into CD34-CD19+clgM+slgM- pre-B cells,
whereas a small proportion of these cells even differentiate into more
mature slgM+ B cells. In contrast, KIT ligand (KL) and granulocyte-
macrophage colony-stimulating factor (GM-CSF) were ineffective in promoting
IL-7-dependent pro-B cell growth and differentiation. Maximal levels of
pro-B cell expansion, generally resulting in 15- to 30-fold increases in
cellularity, were obtained in cultures supplemented with optimal doses of
FL + IL-7 + IL-3. The addition of mouse bone marrow stromal cells further
enhanced the proliferation and differentiation of pro-B cells obtained in
the presence of these three cytokines. Under these conditions, cultures
could be maintained for more than 4 weeks, and in general 40- to 50-fold
increases in cell numbers were observed by 3 weeks of culture. The
percentages of clgM+ and slgM+ B cells increased 1.5- to 3-fold and 2-fold,
respectively, suggesting that stromal cells may provide additional
costimulatory signals for human B- cell growth and differentiation that are
different from IL-7, IL-3, and FL. Collectively, our results indicate that
FL, in contrast to KL, strongly promotes long-term expansion and
differentiation of human pro- B cells in the presence of IL-7 or in
combination of IL-7 and IL-3, which is a novel property of this
hematopoietic growth factor.
Volume 87,
Issue 5,
pp. 1881-1890,
03/01/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
S. Meshinchi and F. R. Appelbaum
Structural and Functional Alterations of FLT3 in Acute Myeloid Leukemia
Clin. Cancer Res.,
July 1, 2009;
15(13):
4263 - 4269.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. K. Parrish, I. Baez, T.-A. Milford, A. Benitez, N. Galloway, J. W. Rogerio, E. Sahakian, M. Kagoda, G. Huang, Q.-L. Hao, et al.
IL-7 Dependence in Human B Lymphopoiesis Increases during Progression of Ontogeny from Cord Blood to Bone Marrow
J. Immunol.,
April 1, 2009;
182(7):
4255 - 4266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Reynaud, N. Lefort, E. Manie, L. Coulombel, and Y. Levy
In vitro identification of human pro-B cells that give rise to macrophages, natural killer cells, and T cells
Blood,
June 1, 2003;
101(11):
4313 - 4321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. R. Comeau, A.-R. Van der Vuurst de Vries, C. R. Maliszewski, and L. Galibert
CD123bright Plasmacytoid Predendritic Cells: Progenitors Undergoing Cell Fate Conversion?
J. Immunol.,
July 1, 2002;
169(1):
75 - 83.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Fry and C. L. Mackall
Interleukin-7: from bench to clinic
Blood,
May 13, 2002;
99(11):
3892 - 3904.
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Shah, L. Oseth, H. Tran, B. Hirsch, and T. W. LeBien
Clonal Variation in the B-Lineage Acute Lymphoblastic Leukemia Response to Multiple Cytokines and Bone Marrow Stromal Cells
Cancer Res.,
July 1, 2001;
61(13):
5268 - 5274.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. M. Crooks, Q.-L. Hao, D. Petersen, L. W. Barsky, and D. Bockstoce
IL-3 Increases Production of B Lymphoid Progenitors from Human CD34+CD38- Cells
J. Immunol.,
September 1, 2000;
165(5):
2382 - 2389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ogawa, E. t. Boekel, and F. Melchers
Identification of CD19-B220+c-Kit+Flt3/Flk-2+cells as early B lymphoid precursors before pre-B-I cells in juvenile mouse bone marrow
Int. Immunol.,
March 1, 2000;
12(3):
313 - 324.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. S. Miller, V. McCullar, M. Punzel, I. R. Lemischka, and K. A. Moore
Single Adult Human CD34+/Lin-/CD38- Progenitors Give Rise to Natural Killer Cells, B-Lineage Cells, Dendritic Cells, and Myeloid Cells
Blood,
January 1, 1999;
93(1):
96 - 106.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Kapp, M. Bhatia, D. Bonnet, B. Murdoch, and J. E. Dick
Treatment of Non-Obese Diabetic (NOD)/Severe-Combined Immunodeficient Mice (SCID) With flt3 Ligand and Interleukin-7 Impairs the B-Lineage Commitment of Repopulating Cells After Transplantation of Human Hematopoietic Cells
Blood,
September 15, 1998;
92(6):
2024 - 2031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. J. McKenna and P. J. Morrissey
Flt3 Ligand Plus IL-7 Supports the Expansion of Murine Thymic B Cell Progenitors That Can Mature Intrathymically
J. Immunol.,
May 15, 1998;
160(10):
4801 - 4809.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. S. Gotze, M. Ramirez, K. Tabor, D. Small, W. Matthews, and C. I. Civin
Flt3high and Flt3low CD34+ Progenitor Cells Isolated From Human Bone Marrow Are Functionally Distinct
Blood,
March 15, 1998;
91(6):
1947 - 1958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. M. Gaffney, J. Lund, and J. S. Miller
FLT-3 Ligand and Marrow Stroma-Derived Factors Promote CD3gamma , CD3delta , CD3zeta , and RAG-2 Gene Expression in Primary Human CD34+LIN-DR- Marrow Progenitors
Blood,
March 1, 1998;
91(5):
1662 - 1670.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. D. Lyman and S. E. W. Jacobsen
c-kit Ligand and Flt3 Ligand: Stem/Progenitor Cell Factors With Overlapping Yet Distinct Activities
Blood,
February 15, 1998;
91(4):
1101 - 1134.
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. P. Veiby, O. J. Borge, A. Martensson, E. X. Beck, A. E. Schade, K. Grzegorzewski, S. D. Lyman, I.-L. Martensson, and S. E.W. Jacobsen
Bidirectional Effect of Interleukin-10 on Early Murine B-Cell Development: Stimulation of flt3-Ligand Plus Interleukin-7-Dependent Generation of CD19- ProB Cells From Uncommitted Bone Marrow Progenitor Cells and Growth Inhibition of CD19+ ProB Cells
Blood,
December 1, 1997;
90(11):
4321 - 4331.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. J. Jarvis, J. E. Maguire, and T. W. LeBien
Contact Between Human Bone Marrow Stromal Cells and B Lymphocytes Enhances Very Late Antigen-4/Vascular Cell Adhesion Molecule-1-Independent Tyrosine Phosphorylation of Focal Adhesion Kinase, Paxillin, and ERK2 in Stromal Cells
Blood,
August 15, 1997;
90(4):
1626 - 1635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. C. Berardi, E. Meffre, F. Pflumio, A. Katz, W. Vainchenker, C. Schiff, and L. Coulombel
Individual CD34+CD38lowCD19-CD10- Progenitor Cells From Human Cord Blood Generate B Lymphocytes and Granulocytes
Blood,
May 15, 1997;
89(10):
3554 - 3564.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta
Extensive Amplification and Self-Renewal of Human Primitive Hematopoietic Stem Cells From Cord Blood
Blood,
April 15, 1997;
89(8):
2644 - 2653.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
