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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 120-127
Novel murine myeloid cell lines that exhibit a differentiation
switch in response to IL-3 or GM-CSF, or to different
constitutively active mutants of the GM-CSF receptor  subunit
Matthew P. McCormack and
Thomas J. Gonda
From the Hanson Centre for Cancer Research and Division of Human
Immunology, Institute of Medical and Veterinary Science, Frome Road,
Adelaide, SA 5000, Australia.
Several activating mutations have recently been described in the
common  subunit for the human interleukin(IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
receptors (hc). Two of these, FI and I374N, result, respectively,
in a 37-amino acid duplication and an isoleucine-to-asparagine
substitution in the extracellular domain. A third, V449E, leads to
valine-to-glutamic acid substitution in the transmembrane domain.
Previous studies have shown that when expressed in murine hemopoietic
cells in vitro, the extracellular mutants can confer factor
independence on only the granulocyte-macrophage lineage
while the transmembrane mutant can do so to all cell types of the
myeloid and erythroid compartments. To further study the signaling
properties of the constitutively active hc mutants, we have
used novel murine hemopoietic cell lines, which we describe in
this report. These lines, FDB1 and FDB2, proliferate in murine
IL-3 and undergo granulocyte-macrophage differentiation in
response to murine GM-CSF. We find that while the transmembrane mutant,
V449E, confers factor-independent proliferation on these cell lines,
the extracellular hc mutants promote differentiation. Hence, in
addition to their ability to confer factor independence on distinct
cell types, transmembrane and extracellular activated hc mutants
deliver distinct signals to the same cell type. Thus, the FDB cell
lines, in combination with activated hc mutants, constitute a
powerful new system to distinguish between signals that determine
hemopoietic proliferation or differentiation. (Blood. 2000;95:120-127)
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