The Characterization, Molecular Cloning, and Expression of a Novel Hematopoietic Cell Antigen From CD34+ Human Bone Marrow Cells

Abstract

The adhesion molecule BEN/SC1/DM-GRASP (BEN) is a marker in the developing chicken nervous system that is also expressed on the surface of embryonic and adult hematopoietic cells such as immature thymocytes, myeloid progenitors, and erythroid progenitors. F84.1 and KG-CAM, two monoclonal antibodies to rat neuronal glycoproteins with similarity to BEN, cross-react with an antigen on rat hematopoietic progenitors, but F84.1 only also recognizes human blood cell progenitors. We have defined the antigen recognized by F84.1 as the hematopoietic cell antigen (HCA). HCA expression was detected on 40% to 70% of CD34+ fetal and adult bone marrow cells and mobilized peripheral blood cells. Precursor cell activity for long-term in vitro bone marrow cell culture was confined to the subset of CD34+ cells that coexpress HCA. HCA is expressed by the most primitive subsets of CD34+ cells, including all rhodamine 123lo, Thy-1+, and CD38−/lo CD34+ adult bone marrow cells. HCA was also detected on myeloid progenitors but not on early B-cell progenitors. We also describe here the cloning and characterization of cDNAs encoding two variants of the human HCA antigen (huHCA-1 and huHCA-2) and of a cDNA clone encoding rat HCA (raHCA). The deduced amino acid sequences of huHCA and raHCA are homologous to that of chicken BEN. Recombinant proteins produced from either human or rat HCA cDNAs were recognized by F84.1, whereas rat HCA but not human HCA was recognized by antirat KG-CAM. Expression of either form of huHCA in CHO cells conferred homophilic adhesion that could be competed with soluble recombinant huHCA-Fc. The molecular cloning of HCA and the availability of recombinant HCA should permit further evaluation of its role in human and rodent hematopoiesis.

Alcam Regulates Long-Term Hematopoietic Stem Cell Engraftment and Self-Renewal

“…ALCAM is known to be expressed on primitive human HSCs [29,30], however, its functional contribution to HSC biology has been unclear. This study provides a comprehensive characterization of the role of Alcam in regulating adult HSC function.…”

“…Notably, ALCAM has been reported to mark a tumor-initiating cell population in prostate cancer and in lung cancer [27,28]. In the hematopoietic system, ALCAM is expressed on activated lymphocytes and monocytes and on primitive human HSCs [29,30]. In addition, Alcam is reportedly required for myeloid colony formation in avian embryonic hematopoietic progenitors [31], and Alcam-expressing endothelial cells can support murine embryonic hematopoiesis [18].…”

Aquaporin‐3 Expression in Human Fetal Airway Epithelial Progenitor Cells

“…Among adhesion molecules, the hyaluronate receptor CD44 was located on all basal cell membranes (Fig. 1E), and CD166, expressed otherwise by embryonic neuroblasts and by hematopoietic stem cells and stromal cells [30][31][32], was found on the apical and baso-lateral membranes of ciliated and secretory cells ( Fig. 1F).…”

Expression of human NDRG2 by myeloid dendritic cells inhibits down-regulation of activated leukocyte cell adhesion molecule (ALCAM) and contributes to maintenance of T cell stimulatory activity

“…Activated leukocyte cell adhesion molecule (ALCAM; CD166), also known as KG-CAM, neurolin, and BEN/DM-GRASP/SC1, is a novel member of the Ig superfamily, which is involved in homophilic adhesion and in binding to CD6 [12,13]. It is expressed on activated leukocytes [14], monocytes [15], hematopoietic progenitor cells [16], bone marrow stromal cells [17], and hematopoiesis-supporting osteoblastic cells [18]. ALCAM-mediated interactions are important during neural development [19], maturation of hematopoietic stem cells in blood-forming tissues [16,17,20], immune responses [21], and tumor progression [22].…”

“…It is expressed on activated leukocytes [14], monocytes [15], hematopoietic progenitor cells [16], bone marrow stromal cells [17], and hematopoiesis-supporting osteoblastic cells [18]. ALCAM-mediated interactions are important during neural development [19], maturation of hematopoietic stem cells in blood-forming tissues [16,17,20], immune responses [21], and tumor progression [22]. Although ALCAM was shown to mediate homotypic and heterotypic cell-cell clustering through homophilic (ALCAM-ALCAM) and heterophilic (ALCAM-CD6) interaction [14], Hassan et al [23] demonstrated recently that homophilic interaction was approximately 100 times weaker than heterophilic interaction.…”