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Differential expression of receptors for interleukin-3 on subsets of
CD34-expressing hematopoietic cells of rhesus monkeys
AW Wognum, TP Visser, MO de Jong, T Egeland and G Wagemaker
Department of Hematology, Erasmus Universiteit, Rotterdam, The Netherlands.
The target cell specificity of interleukin-3 (IL-3) was examined by flow
cytometric analysis of IL-3 receptor (IL-3R) expression on rhesus monkey
bone marrow (BM) cells using biotinylated IL-3. Only 2% to 5% of
unfractionated cells stained specifically with the biotinylated IL-3 and
most of these cells were present within the CD34+ subset. IL-3Rs were
detected on small CD34dull/RhLA-DRbright/CD10+/CD27+/CD2-/++ +CD20- cells,
which probably represent B-cell precursors. IL-3R+ CD34- BM cells, which
were detected at low frequencies, consisted of small
CD20dull/surface-IgM+/RhLA-DR+ cells. These cells represented immature B
lymphocytes, whereas CD20bright mature B cells were IL-3R-. The highest
IL-3R levels were detected on CD34dull/RhLA-DRbright blast-like cells.
These cells differentiated into monocytes, neutrophils, and basophils after
IL-3 and/or granulocyte-macrophage colony-stimulating factor (GM-CSF)
stimulation in vitro. The CD34bright/IL-3R- subset contained all clonogenic
erythroid and myeloid progenitors (burst- forming unit-erythroid and
colony-forming unit-culture), whereas CD34bright/IL-3Rdull cells
differentiated into monocytes, neutrophils, and erythroid cells after
shorter culture periods. This finding showed that IL-3R expression
increases during monocyte and granulocyte differentiation. Results of
three-color experiments indicated that IL- 3Rs are expressed on
CD34bright/RhLA-DRbright cells as well as on CD34bright/RhLA-DRdull cells,
with the latter population expression approximately twofold to threefold
lower IL-3R levels. A large fraction (> 30%) of single-cell/well-sorted
CD34bright/RhLA-DRdull cells formed multilineage colonies after 2 to 4
weeks of stimulation with IL-3, GM- CSF, Kit ligand, and IL-6. Individual
colonies contained cells that still expressed CD34 as well as
differentiated monocytes, granulocytes, and erythroid cells. These results
confirmed that the CD34bright/RhLA- DRdull subset was enriched for
immature, multipotent progenitor cells, whereas the
CD34bright/RhLA-DRbright population mainly contained lineage-committed
precursors. The results are consistent with the concept that IL-3Rs are
induced at very early stages of hematopoiesis, as identified by high
expression of CD34 and low expression of RhLA-DR. IL-3R expression
continues to be low during differentiation into lineage-committed
progenitors; gradually increases on differentiating progenitor cells for B
cells, granulocytes, monocytes, and, possibly also, erythrocytes; but
finally declines to undetectable levels during terminal differentiation
into mature cells of all lineages in peripheral blood, with the exception
of basophils.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 86,
Issue 2,
pp. 581-591,
07/15/1995
Copyright © 1995 by The American Society of Hematology
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