Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Query: UNIPROT:P10721 (
c-kit
)
6,575
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Dendritic cells (DC) represent key regulators of the immune system, yet their development from hemopoietic precursors is poorly defined. In this study, we describe an in vitro system for amplification of a Flt3(+)CD11b(+) progenitor from mouse bone marrow with specific cytokines. Such progenitor cells develop into both CD11b(+) and CD11b(-) DC, and CD8alpha(+) and CD8alpha(-) DC in vivo. Furthermore, with GM-CSF, these progenitors synchronously differentiated into fully functional DC in vitro. This two-step culture system yields homogeneous populations of Flt3(+)CD11b(+) progenitor cells in high numbers and allows monitoring the consecutive steps of DC development in vitro under well-defined conditions. We used phenotypic and functional markers and transcriptional profiling by DNA microarrays to study the Flt3(+)CD11b(+) progenitor and differentiated DC. We report here on an extensive analysis of the surface Ag expression of Flt3(+)CD11b(+) progenitor cells and relate that to surface Ag expression of hemopoietic stem cells. Flt3(+)CD11b(+) progenitors studied exhibit a broad overlap of surface Ags with stem cells and express several stem cell Ags such as Flt3, IL-6R,
c-kit
/SCF receptor, and
CD93
/AA4.1, CD133/AC133, and CD49f/integrin alpha(6). Thus, Flt3(+)CD11b(+) progenitors express several stem cell surface Ags and develop into both CD11b(+) and CD11b(-) DC, and CD8alpha(+) and CD8alpha(-) DC in vivo, and thus into both of the main conventional DC subtypes.
...
PMID:Progressive and controlled development of mouse dendritic cells from Flt3+CD11b+ progenitors in vitro. 1572 61
Deregulated expression of c-myc and bcl-xL is long known to generate transformed B cells in humans and mice. We overexpressed these genes to induce in vitro and in vivo differentiation of fetal liver-derived mouse pre-BI cells to B1-lineage pre-BII-like, immature and mature B-cell lines, and to Ig-secreting cells. In vitro, doxycycline-controlled c-myc/bcl-xL-overexpressing CD19
+
CD93
+
c-kikt
+
IgM
-
pre-BI cells differentiate to and survive as CD19
+
CD93
+
c-kit
-
IgM
+
immature B1 cells. Timed CpG stimulation of these oncogene-overexpressing pre-B or immature B1 cells generates either CD19
+
CD93
low
c-kit
-
IgM
-
SLC
-
pre-BII-like or IgM
+
MHCII
+
CD73
+
CD80
+
CD40
+
mature B1-cell lines and IgM-secreting B1 cells in vitro and fixes their state of differentiation. All cell lines are clonable, but a majority of immature and mature B1-cell clones eventually reach a nonproliferating, surviving G
0
-state. Transplanted in vivo, c-myc/bcl-xL-overexpressing pre-B cells expand to mature B1 cells, and to IgM- and IgA-secreting plasmablasts and plasma cells. Within 2 months, plasmablasts have expanded most prominently in BM and spleen, indicating that the host selectively expanded development of these transformed plasma cells. The sIgM
+
B1-cell lines and clones offer the possibility to study their roles in the development of B1-Ab repertoires, of B1-cell-mediated autoimmune diseases and of B1-cell malignancies.
...
PMID:Generation of precursor, immature, and mature murine B1-cell lines from c-myc/bcl-xL-overexpressing pre-BI cells. 2829 14
