Lymphoid Priming in Human Bone Marrow Begins Prior to CD10 Expression with Up-Regulation of L-selectin

Department of Pathology & Laboratory Medicine, University of California, Los Angeles, California, USA.
Nature Immunology (Impact Factor: 24.97). 09/2012; 13(10):963-71. DOI: 10.1038/ni.2405
Source: PubMed

ABSTRACT Expression of the cell-surface antigen CD10 has long been used to define the lymphoid commitment of human cells. Here we report a unique lymphoid-primed population in human bone marrow that was generated from hematopoietic stem cells (HSCs) before onset of the expression of CD10 and commitment to the B cell lineage. We identified this subset by high expression of the homing molecule L-selectin (CD62L). CD10(-)CD62L(hi) progenitors had full lymphoid and monocytic potential but lacked erythroid potential. Gene-expression profiling placed the CD10(-)CD62L(hi) population at an intermediate stage of differentiation between HSCs and lineage-negative (Lin(-)) CD34(+)CD10(+) progenitors. CD62L was expressed on immature thymocytes, and its ligands were expressed at the cortico-medullary junction of the thymus, which suggested a possible role for this molecule in homing to the thymus. Our studies identify the earliest stage of lymphoid priming in human bone marrow.

    • "This pathway involves sequential loss of developmental potential from a progenitor that can produce granulocytes , monocytes, and DCs (hGMDPs), to one that produces monocytes and DCs (hMDPs), to a committed DC progenitor that produces cDCs and pDCs (hCDPs). Others have shown that human GMPs, CLPs, and LMPPs can produce human DCs (Chicha et al., 2004; Ishikawa et al., 2007; Kohn et al., 2012). Our findings are not inconsistent with these observations because GMPs and LMPPs are heterogeneous groups of cells that contain subpopulations with the cell surface features of DC progenitors , as revealed by cross-phenotyping (Fig. 5 "
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    • "These include CCR7 and its ligand (CCL19/21), CCR9 and its ligand (CCL25) [25], [26], and PSGL1 [27]. In humans, the mechanisms of thymus colonization have been less studied, but similar chemokines may be involved, at least during the fetal and perinatal periods [8], [10], [28]. In our study, whereas PSGL1 expression was not modified (Data not shown), CCR7 and CCR9 mRNA expression was reduced after allo-HSCT, even in the absence of aGVHD. "
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    • "To further understand the mechanisms by which LPA induced myeloid differentiation, we explored LPA receptor expression on specific hematopoietic stem and progenitor populations. Real time RT-PCR was performed on freshly isolated CD34+CD38-lin- cells (enriched for HSPC), CD34+lin-CD45RA-IL3Ralo common myeloid progenitors (CMP), and CD34+lin-CD10+ common lymphoid progenitors (CLP) (a population with predominantly B cell potential [15] (Fig. 3A). Expression of all six LPA receptors was higher in CMP than either HSPC or CLP (p<0.05 for LPAR 1,2,4 and 6). "
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