Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.148 (Thy1)
 1,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

v-mpl is a constitutively activated, truncated form of a cytokine receptor that has been transduced in a murine retrovirus, the myeloproliferative leukemia virus (MPLV). Expression of this oncogene results in the factor-independent proliferation of myeloid, erythroid, megakaryocytic, and mast precursor cells, which retain the ability to differentiate. However, no lymphoid disease was ever reported. To determine whether MPLV could infect and transform very early B cells and their precursors (BCPs), lymphoid long-term bone marrow cultures were infected with a helper-free MPLV. Within 3 wk after infection, highly proliferating BCPs could be isolated. These cells were able to clone spontaneously in semi-solid cultures, grown in the absence of feeder cell layer or exogenous growth factor and rapidly produced tumors after s.c. injection into synegic irradiated mice. In addition, MPLV transformation of pre-B cells led to the induction of an autocrine activity. Immunophenotypic and molecular analysis indicated that MPLV transformed early pro-B, pro-B, and pre-B cells, according to the expression of HSA, CD43, B220, Thy1, s-IgM and BP1 Ags, and to the rearrangements of Ig genes. Interestingly, MPLV-transformed BCPs expressed Mac1 Ag without acquiring further characteristics of macrophagic differentiation. Although the v-mpl cytoplasmic domain is devoid of tyrosine kinase consensus sequence, MPLV-transformed pre-B cells contained a major approximately 105-kDa tyrosine-phosphorylated protein that was not detected in uninfected cells or in cells transformed by the Abelson viral oncogene (v-abl). These results demonstrate that, like v-abl, the truncated cytokine receptor v-mpl is able to transform BCPs in vitro and suggest that the oncogenic transformation of BCPs by either v-mpl or v-abl use different pathways.
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PMID:In vitro transformation of murine pro-B and pre-B cells by v-mpl, a truncated form of a cytokine receptor. 783 43

Mice inoculated with the murine AIDS (MAIDS)-defective virus develop severe B and T cell dysfunctions. The primary event in the development of this disease is the infection and polyclonal expansion of the target cells of this defective virus, which have been reported to belong to the B cell lineage. To further study the central role that these cells play in the development of MAIDS, we attempted to establish MAIDS-defective virus-infected B cell lines in vitro. We succeeded in establishing two cell lines, SD1 and CSTB5, from the enlarged organs of C57BL/6 mice inoculated with helper-free stocks of the MAIDS-defective virus. Both cell lines are not transplantable in syngeneic C57BL/6 mice or in nude or CD8-/- mice and are apparently not malignant. They both belong to the B lineage, as their immunoglobulin (Ig) genes, but not the T cell receptor (TcR) beta locus, are rearranged, suggesting that they are relatively mature B cells. However, analysis of cell surface marker expression by FACS revealed a surface phenotype similar to that of pre-B cells (MHC I+, MHC II+, B7.2+, sIgM-, sIgG-, kappa-, B220-, CD5-, Thy1.2-, TcR-, CD3-, CD4-, CD8-, Mac-1-, 33D1-). Additionally, the CSTB5 cells express CD40 and the SD1 cells express CD43. Both cell lines contain the MAIDS-defective provirus and express the expected 4.2-kb viral RNA and the corresponding Pr60gag protein. The CSTB5 cells are nonproducer, while the SD1 cell line produces what appears to be an endogenous MuLV. The phenotype of these cell lines is very similar to what is known about the target B cells of this virus in vivo. These new established cell lines are likely to be useful in elucidating the mechanism(s) by which the MAIDS-defective virus causes its target B cells to proliferate and induce T cell anergy in infected animals.
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PMID:Establishment of MAIDS-defective virus-infected B cell lines and their characterization. 960 99

To ensure the B cell differentiation stage specificity of the intronic Emu element and of the locus control region (LCR) that lies downstream of the IgH chain locus, we generated transgenic mice harboring a V(H) promoter-GFP reporter gene linked to the 3'LCR region and the Emu element. By flow cytometry, GFP(+) lymphocytes were observed amongst pro-B cells (B220(+)CD43(+)CD117(+)) and at all stages of differentiation up to mature B cells (B220(+)IgM(+)IgD(+)). Expression was strictly confined to cells committed to the B lymphocyte lineage as judged by the lack of GFP(+)Thy1,2(+) cells (T lymphocytes) and GFP(+)B220(-)CD117(+)CD43(+) cells (uncommitted lymphohematopoietic progenitors). Therefore, the Emu-GFP-3'LCR transgene is not expressed by hematopoietic stem cells, begins its expression in pro-B cells and is specifically active at all stages of B cell maturation. The combination of 3' and 5' IgH regulatory elements thus appears as a potentially useful cassette in transgenes that require a stringent and early B lineage-specific expression.
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PMID:Combination of 3' and 5' IgH regulatory elements mimics the B-specific endogenous expression pattern of IgH genes from pro-B cells to mature B cells in a transgenic mouse model. 1457 1

Notch signaling regulates multiple cell fate decisions by hematopoietic precursors. To address whether different amounts of Notch ligand influence lineage choices, we cultured murine bone marrow lin(-)Sca-1(+)c-kit+ cells with increasing densities of immobilized Delta1(ext-IgG) consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG1. We found that relatively lower densities of Delta1(ext-IgG) enhanced the generation of Sca-1(+)c-kit+ cells, Thy1(+)CD25+ early T cell precursors, and B220(+)CD43(-/lo) cells that, when cocultured with OP9 stroma cells, differentiated into CD19+ early B cell precursors. Higher densities of Delta1(ext-IgG) also enhanced the generation of Sca-1(+)c-kit+ precursor cells and promoted the development of Thy1(+)CD25+ cells, but inhibited the development of B220(+)CD43(-/lo) cells. Analyses of further isolated precursor populations suggested that the enhanced generation of T and B cell precursors resulted from the effects on multipotent rather than lymphoid-committed precursors. The results demonstrate the density-dependent effects of Delta1 on fate decisions of hematopoietic precursors at multiple maturational stages and substantiate the previously unrecognized ability of Delta1 to enhance the development of both early B and T precursor cells.
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PMID:Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells. 1585 88