Development of human lymphohematopoiesis defined by CD34 and CD81 expression

Human blood cells, except for erythrocytes and platelets, express CD81, a member of the transmembrane 4 superfamily (TM4SF). CD81 is also expressed on most of human immature hematopoietic cells, CD34(+) cells, which are divided into three populations according to the expression of CD34 and CD81; CD34(+) CD81(+) , CD34(+) CD81(High) and CD34(Low) CD81(+) . Myeloid and lymphoid progenitors exist in the CD34(+) CD81(+) population, and megakaryocytic progenitors are only in CD34(Low) CD81(+) population. Erythroid and multipotential progenitors are shared by CD34(+) CD81(+) and CD34(Low) CD81(+) populations, but multipotential progenitors in the CD34(+) CD81(+) population have already lost most of their myeloid potential. NK cells and mast cells can be generated from all three populations. Long-term repopulating (LTR) lymphohematopoietic stem cells are present in the CD34(+) CD81(+) population. Based on these findings, we propose a model for the development of CD34(+) CD81(+) lymphohematopoietic stem cells. Along the differentiation cascade from CD34(+) CD81(+) lymphohematopoietic stem cells, there appear to be pathways to CD34(Low) CD81(+) or CD34(+) CD81(High) cells, even if they are indirect. CD34(Low) CD81(+) pathways define the loss of LTR ability, and lymphoid and myeloid potentials, whereas CD34(+) CD81(High) pathways represent the exclusive commitment to NK cells and mast cells.