Research Article: CD32b defines distinct dendritic cell lineages generated from the culture of bone marrow with GM-CSF
Abstract:
Culturing bone marrow (BM) with granulocyte macrophage-colony stimulating factor (GM-CSF) is the most commonly used standard method of generating mouse dendritic cells (DCs) in vitro , although the development of those MHC II hi GM-CSF–induced DCs (GM-DCs) remains poorly elucidated. Here, we have characterized that in vitro -generated GM-DCs from the BM comprise two distinct subsets distinguished by the expression of CD32b, arising at a different time from a separate progenitor lineage. Monocyte-dendritic cell progenitors (MDPs) give rise to CD32b - GM-DCs within the first week of the BM culture, while granulocyte-monocyte progenitors (GMPs) generate CD32b + GM-DCs at a slower rate and become numerically dominant in the later stages. In addition, there exist separate populations of pre-GM-DCs in the BM culture; Ly6C - CD32b - MHC II int pre-GM-DCs for CD32b - GM-DCs and Ly6C - CD32b + MHC II int pre-GM-DCs for CD32b + GM-DCs. These two GM-DC subsets also exhibit distinct functions; specifically, CD32b + GM-DCs have enhanced capacity to stimulate CD4 + T cells. Notably, when adoptively transferred to mice treated with GM-CSF, GMPs selectively generate CD32b + GM-DCs in vivo with delayed kinetics, compared to MDPs that give rise to heterogeneous GM-DC subsets in vivo rather quickly. Therefore, we have identified CD32b as a marker to differentiate two developmentally and functionally distinct GM-DCs, thus demonstrating the heterogeneity of GM-DCs, for the first time.
Introduction:
Dendritic cells (DCs) are professional antigen-presenting cells that bridge innate and adaptive immunity by initiating T cell responses to pathogens ( 1 ). DCs are broadly classified into plasmacytoid DCs (pDCs) and classical DCs (cDCs) based on their developmental origins and functions. pDCs, derived from common lymphoid progenitors (CLPs), are specialized for antiviral responses and characterized by their production of type I interferons ( 2 ). cDCs originate from myeloid progenitors and are further subdivided…
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