Functional characterization of human CD34+ cells that express low or high levels of the membrane antigen CD111 (nectin 1)

Nectins are recently described adhesion molecules that are widely expressed on many tissues, including the hematopoietic tissue. Nectin 1 (CD111) is expressed on a higher proportion of mobilized peripheral blood (mPB) than cord blood ( CB) CD34(+) cells, and of CD34(+)/CD38(+) cells when compared with CD34(+)/ CD38(-) cells. We studied functional properties of human CB and mPB CD34+ cells that express low or high levels of CD111. CD34(+)/CD111(dim) cells contain a higher proportion of cells in G0/ G1 phase than CD34(+)/ CD111(bright) cells. CD34(+)/ CD111(bright) cells contain more erythroid progenitors: CFU-E, than their counterparts, which on the opposite contain more HPP-CFC. Limiting dilution analyses demonstrate a higher frequency of immature progenitors: cobblestone-area colony-forming cells, in CD34(+)/ CD111(dim) than in CD34(+)/ CD111 bright cells. In vitro differentiation assays demonstrate a higher frequency of B-, T- and dendritic-cell precursors, but less NK-cell precursors in CD34(+)/CD111(dim) cells. Evaluation of engraftment in NOD-SCID mice shows that SCID repopulating cells are more frequent among mPB CD34(+)/ CD111(dim) cells. Liquid culture of CD34(+)/ CD111(dim) cells with erythropoietin shows that CD111 expression increases simultaneously with CD36, following CD71 and before glycophorin A expression. In conclusion, immature human hematopoietic progenitors express low levels of CD111 on their surface. During erythroid differentiation CD34(+) cells acquire higher levels of the CD111 antigen.