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Flow cytometric assessment of human MIC2 expression in bone marrow, thymus,
and peripheral blood
MN Dworzak, G Fritsch, P Buchinger, C Fleischer, D Printz, A Zellner, A Schollhammer, G Steiner, PF Ambros and H Gadner
Children's Cancer Research Institute, St Anna Kinderspital, Vienna,
Austria.
The cell-surface expression of the MIC2 antigen defined by the monoclonal
antibody 12E7 was investigated on human leukocytes in bone marrow (BM),
thymus, and peripheral blood (PB) using multiparameter flow cytometry and
cell sorting. In contrast to preceding reports, we found that the MIC2
antigen is not restricted to T cells and monocytes. We show that it is also
expressed in the B cell and in the granulocytic lineage, the levels of
expression being related to distinct maturational stages. CD34+ cells of BM
were found to express the antigen at high levels. Along the granulocytic
maturation pathway from CD34+CD33+ blasts to mature granulocytes, MIC2
densities appeared progressively reduced with a considerable decline at the
myelocyte stage. In B lymphopoiesis, the earliest CD34+ CD10+ B-cell
precursor (BCP) cells, further subdivided by expression of CD19, displayed
the highest MIC2 density of BM leukocytes. All later BCP stages showed
lower MIC2 expression levels, with a remarkable reduction concomitant with
loss of the CD34 antigen at the CD10+CD20- surface mu-chain- stage, and a
subsequent slight upregulation along with maturation to CD10-CD20high
surface mu-chain+ BCPs. The brightest MIC2 expression of all cells tested
was displayed by the most immature thymic T-lineage cells characterized by
the antigenic profile CD34weakor- CD7++ surface CD3-CD1a(weak) CD4weak
CD8-or weak. Common thymocytes stained slightly less intense with 12E7,
whereas all subsequent stages of T-lineage cells in thymus, PB, or BM
showed markedly reduced MIC2 levels. Mature peripheral CD4+ as well as CD8+
T cells displayed a bimodal distribution of MIC2. In the CD4+ population,
the distinct MIC2 levels were related to the well-studied functional
subdivision by differential expression of CD45 isoforms, the
helper-inducer/memory subset showing higher MIC2 expression than
helper-suppressor/naive CD4+ T cells. Similarly high MIC2 densities were
found on CD16+ natural killer cells and on CD14+ monocytes, whereas mature
peripheral B cells exhibited low or intermediate expression, and
granulocytes exhibited no or only dim expression. These results document
that the MIC2 antigen (1) is expressed on all leukocyte lineages; (2) is
differentially expressed during T- and B-lymphoid, as well as granulocytic
maturation; (3) shows highest expression in the most immature lymphocytic
and granulocytic developmental stages; and (4) is also differentially
expressed on functional T-cell subsets. We speculate that these
observations imply a functional significance of MIC2 in the network of
hematopoietic adhesion pathways.
Volume 83,
Issue 2,
pp. 415-425,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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