Immunophenotypical, morphologic, and functional characterization of maturation-associated plasmacytoid dendritic cell subsets in normal adult human bone marrow

BACKGROUND: Information about maturation of plasmacytoid dendritic cell precursors (pre-pDCs) in normal bone marrow (BM) remains limited. STUDY DESIGN AND METHODS: Immunophenotypical, morphologic, and functional changes associated with maturation of pre-pDCs were analyzed in adult normal human BM (n = 45). RESULTS: Three pre-pDC maturation stages, with an increasingly higher degree of maturity, were systematically identified: CD34++/HLA-DR++/+++/CD123++/CD45+/++ (Stage I), CD34+/HLA-DR+/++/CD123++/+++/CD45+/++ (Stage II), and CD34-/HLA-DR++/CD123++/+++/CD45++ (Stage III) cells. Lymphoid- and early myeloid-associated molecules, as well as CD86, were coexpressed in Stage I pre-pDCs, being down regulated afterward. CD304 and CD85j appeared in Stage I, progressively increasing their levels thereafter. Interestingly, cutaneous lymphocyte-associated antigen was heterogeneously expressed throughout the maturation, particularly in Stage I pre-pDCs. The morphologic appearance of Stage I pre-pDCs was consistent with their undifferentiated stage, while Stage II/III cells showed morphologic features of more differentiated cells. From the functional point of view, only Stage II and Stage III pre-pDCs were capable of inducing allogeneic T-cell proliferation, the later subset also showing interferon-gamma secretion; in contrast, Stage I pre-pDCs showed the highest endocytic ability. CONCLUSION: In summary, three maturation stages of pre-pDCs can be identified in adult normal BM, which show unique phenotypical, morphologic, and functional characteristics; these results provide a frame of reference for a better understanding of pDC malignancies.