Interleukin-3Ralpha+ myeloid dendritic cells and mast cells develop simultaneously from different bone marrow precursors in cultures with interleukin-3.

Abstract

The distinct developmental routes of dendritic cells and mast cells from murine bone marrow cultures with interleukin-3 are unclear. We found that short-term bone marrow cultures with interleukin-3 after 8-10 d consist of about 10%-30% dendritic cells and 70%-90% mast cell precursors, and only after 4-6 wk do homogeneous populations of mast cells emerge. Phenotypical and functional analysis of interleukin-3/dendritic cells revealed a high similarity with myeloid dendritic cells generated with granulocyte-macrophage colony stimulating factor in the expression of myeloid dendritic cell markers (CD11c+ B220- CD8alpha- CD11b+), major histocompatibility complex II and costimulatory molecules, endocytosis, maturation potential, interleukin-12 production, and T cell priming. Interleukin-3/dendritic cells expressed higher levels of interleukin-3 receptor, however. To dissect the interleukin-3/dendritic cell and mast cell development, we sorted fresh bone marrow cells into six subsets by the antibodies ER-MP12 (CD31) and ER-MP20 (Ly-6C). Both interelukin-3/dendritic cells and granulocyte-macrophage colony stimulating factor/dendritic cells develop from the same bone marrow populations, including the ER-MP12neg, ER-MP20high bone marrow monocytes. In contrast, mast cells only developed from ER-MP12(int+high), ER-MP20neg bone marrow cell subsets, indicating that different precursors exist for interleukin-3/dendritic cells and mast cells. Established mast cell cultures could not be converted to dendritic cells or stimulated to express major histocompatibility complex II molecules in vitro or home to lymph node T cell areas in vivo. In summary, we show that dendritic cells generated from bone marrow precursors with interleukin-3 are clearly myeloid and develop via a different pathway compared to bone marrow mast cells.