Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood

Abstract

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.

CD99 is a novel prognostic stromal marker in non‐small cell lung cancer

“…Furthermore, CD99 expression was observed in normal tissues. 34 Presently, CD99 is best established as a diagnostic marker for Ewing sarcoma and primitive neuroectodermal tumours, 35 although CD99 immunoreactivity has also been shown in several other malignancies, e.g., hematopoietic neoplasm, 36 synovial sarcoma, 37 solitary fibrous tumours, 38 testicular and ovarian sex cord tumours 39,40 and breast cancer. 41 In association studies, loss of CD99 was found to be associated to poor prognosis in patients with osteosarcoma, 13 pancreatic endocrine tumours 42 and gastric adenocarcinoma.…”

T‐Cell lymphoblastic lymphoma presenting as bilateral multinodular breast masses: A case report and review of the literature

“…CD99 is expressed in 80-90% of T-LBLs [32], and appears to correlate with TdT expression [33]. In the thymus, CD99 is expressed at high levels not only in very early T-lineage cells but also in CD4+CD8+ or double-positive (DP) thymocytes [34]. The function of this protein at the early DN stage of development is not known, but a role in the mediation of apoptosis of maturing (DP) thymocytes was demonstrated [35].…”

Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells

“…CD34 does not specifically identify HPC subpopulations responsible for short-and long-term engraftment (8,31). With respect to short-term engraftment, which is the major goal in the supportive use of HPCs, the transplanted numbers of CD34 ϩ ,33 Ϫ cells have been reported to correlate significantly better with the rates of neutrophil reconstitution than those of the entire CD34 ϩ population (27).…”