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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 849-866
CD164, a Novel Sialomucin on CD34+ and Erythroid
Subsets, Is Located on Human Chromosome 6q21
Suzanne M. Watt,
Hans-Jörg Bühring,
Irene Rappold,
James Yi-Hsin Chan,
Jane Lee-Prudhoe,
Tania Jones,
Andrew C.W. Zannettino,
Paul J. Simmons,
Regis Doyonnas,
Denise Sheer, and
Lisa H. Butler
From the MRC Molecular Haematology Unit, Institute of Molecular
Medicine, The John Radcliffe Hospital, Oxford, UK; Medizinische
Universitatsklinik II, University of Tübingen, Tübingen,
Germany; Human Cytogenetics Laboratory, Imperial Cancer Research Fund,
London, UK; and the Hanson Centre for Cancer Research, Matthew Roberts
Laboratory, Instiute of Medical and Veterinary Sciences, Adelaide,
South Australia.
CD164 is a novel 80- to 90-kD mucin-like molecule expressed by human
CD34+ hematopoietic progenitor cells. Our previous
results suggest that this receptor may play a key role in hematopoiesis
by facilitating the adhesion of CD34+ cells to bone
marrow stroma and by negatively regulating CD34+
hematopoietic progenitor cell growth. These functional effects are
mediated by at least two spatially distinct epitopes, defined by the
monoclonal antibodies (MoAbs), 103B2/9E10 and 105A5. In this report, we
show that these MoAbs, together with two other CD164 MoAbs, N6B6 and
67D2, show distinct patterns of reactivity when analyzed on
hematopoietic cells from normal human bone marrow, umbilical cord
blood, and peripheral blood. Flow cytometric analyses revealed that, on
average, 63% to 82% of human bone marrow and 55% to 93% of cord
blood CD34+ cells are CD164+, with
expression of the 105A5 epitope being more variable than that of the
other identified epitopes. Extensive multiparameter flow cytometric
analyses were performed on cells expressing the 103B2/9E10 functional
epitope. These analyses showed that the majority (>90%) of
CD34+ human bone marrow and cord blood cells that were
CD38lo/ or that coexpressed AC133, CD90(Thy-1),
CD117(c-kit), or CD135(FLT-3) were
CD164(103B2/9E10)+. This CD164 epitope was generally
detected on a significant proportion of
CD34+CD71lo/ or
CD34+CD33lo/ cells. In accord with our
previous in vitro progenitor assay data, these phenotypes suggest that
the CD164(103B2/9E10) epitope is expressed by a very primitive
hematopoietic progenitor cell subset. It is of particular interest to
note that the CD34+CD164(103B2/9E10)lo/
cells in bone marrow are mainly CD19+ B-cell precursors,
with the CD164(103B2/9E10) epitope subsequently appearing on
CD34lo/CD19+ and
CD34lo/CD20+ B cells in bone marrow, but
being virtually absent from B cells in the peripheral blood.
Further analyses of the
CD34lo/CD164(103B2/9E10)+ subsets
indicated that one of the most prominent populations consists of
maturing erythroid cells. The expression of the CD164(103B2/9E10) epitope precedes the appearance of the glycophorin C, glycophorin A,
and band III erythroid lineage markers but is lost on terminal differentiation of the erythroid cells. Expression of this
CD164(103B2/9E10) epitope is also found on developing myelomonocytic
cells in bone marrow, being downregulated on mature neutrophils but
maintained on monocytes in the peripheral blood. We have extended these
studies further by identifying Pl artificial chromosome
(PAC) clones containing the CD164 gene and have used these to localize
the CD164 gene specifically to human chromosome 6q21.
© 1998 by The American Society of Hematology.
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