The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal-cell-independent expansion and differentiation of human fetal pro-B cells in vitro

Reiko Namikawa, Marcus O. Muench, Jan E. De Vries, Maria Grazia Roncarolo

Research output: Contribution to journalArticle

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Abstract

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+cIgM+sIgM- pre-B cells, whereas a small proportion of these cells even differentiate into more mature sIgM+ 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 proB 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 cIgM+ and sIgM+ 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.

Original languageEnglish
Pages (from-to)1881-1890
Number of pages10
JournalBlood
Volume87
Issue number5
Publication statusPublished - Mar 1 1996

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Interleukin-7
B-Lymphoid Precursor Cells
Stromal Cells
Cells
Ligands
Interleukin-3
Cell growth
Cell Differentiation
B-Lymphocytes
Bone
Growth
Cytokines
Granulocyte-Macrophage Colony-Stimulating Factor
In Vitro Techniques
Mesenchymal Stromal Cells
Intercellular Signaling Peptides and Proteins
Cell Count
Bone Marrow
Serum

ASJC Scopus subject areas

  • Hematology

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The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal-cell-independent expansion and differentiation of human fetal pro-B cells in vitro. / Namikawa, Reiko; Muench, Marcus O.; De Vries, Jan E.; Roncarolo, Maria Grazia.

In: Blood, Vol. 87, No. 5, 01.03.1996, p. 1881-1890.

Research output: Contribution to journalArticle

Namikawa, Reiko ; Muench, Marcus O. ; De Vries, Jan E. ; Roncarolo, Maria Grazia. / The FLK2/FLT3 ligand synergizes with interleukin-7 in promoting stromal-cell-independent expansion and differentiation of human fetal pro-B cells in vitro. In: Blood. 1996 ; Vol. 87, No. 5. pp. 1881-1890.
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