Abstract
The dendritic cell (DC) compartment comprises subsets of cells with distinct phenotypes. Previously this lab reported methodology for hematopoiesis of dendritic-like cells in vitro dependent on a murine splenic stromal cell line (5G3). Co-cultures of lineage-depleted bone marrow (Lin− BM) over 5G3 continuously produced a distinct population of dendritic-like “L-DC” for up to 35 days. Here the progenitor of L-DC is investigated in relation to known BM-derived hematopoietic progenitors. It is shown here that L-DC-like cells also derive from the CD150+Flt3− long-term reconstituting-hematopoietic stem cells (HSC), and also from the Flt3+ multipotential progenitor subset in BM. Lin− BM co-cultures also produce a transient population of cells resembling conventional (c) DC. Production of cDC-like cells is shown here to be transient and M-CSF dependent, and also appears following co-culture of described common dendritic progenitors or monocyte dendritic progenitors over 5G3. BM cells from C57BL/6-flt3Ltm1lmx and C57BL/6-Csf2tm1Ard mice which lack cDC precursors and monocytes, are shown here to contain L-DC progenitors which can seed 5G3 co-cultures. L-DC are functionally distinct cells, in that they arise independently of M-CSF, and by direct differentiation from HSC.
Highlights
Dendritic cells (DCs) are professional antigen presenting cells required for induction of adaptive immune responses against invading pathogens, and for maintaining tolerance to self antigens
L-DC AND cDC-LIKE CELLS ARISE FROM DISTINCT PROGENITORS IN bone marrow (BM) Previous reports from this lab showed that splenic stroma can support longterm development of L-DC from lineage-depleted bone marrow (Lin− BM) along with a transient population of cDC-like cells [6, 8]
LT-hematopoietic stem cells (HSC) and multipotential progenitors (MPP) differed in expression of CD150 and Flt3, and did not express CD115
Summary
Dendritic cells (DCs) are professional antigen presenting cells required for induction of adaptive immune responses against invading pathogens, and for maintaining tolerance to self antigens. A distinct subset of dendritic-like cells, namely “L-DC,” was recently characterized in murine spleen in the steady-state and produced in co-cultures of mouse spleen or bone marrow (BM) cells over stroma [4,5,6, 31]. L-DC produced in vitro or isolated from spleen have been shown to have powerful capacity to cross-present antigen to CD8+ T cells [7, 9]. They can be distinguished functionally and phenotypically from both DC and monocyte subsets in spleen [9]. Development of L-DC from progenitors has been characterized in terms of dependency for known cytokines which support the development of other known DC and myeloid subsets
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