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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TCR-beta gene rearrangement or expression is necessary and sufficient for the progression of early alpha beta thymocyte differentiation from the CD3-CD4-CD8- triple negative (TN)3 to the CD4+CD8+ double positive stage. The onset of TCR-beta rearrangement is currently thought to occur gradually. Some thymocytes were reported to be rearranged at the earliest (CD44+CD25-) TN stage, whereas other thymocytes did not initiate TCR-beta rearrangement until the latest (CD44-CD25-) TN stage. Here, we have isolated subsets of TN thymocytes on the basis of surface expression of CD44 and CD25, with c-kit as an additional marker. We present a revised model of early T cell development in which TCR-beta and TCR-gamma rearrangements occur abruptly, at the CD44lowCD25+ c-kitlowTN stage. A high level of c-kit expression defines pro-T cells which have not yet rearranged their TCR genes. Germ-line TCR-beta transcripts, and transcripts of recombination activating genes (RAG)-1 and 2, are detected before TCR-beta gene rearrangement. Analyses of TN thymocytes of RAG-1 mutant mice, and of various TCR mutant and TCR transgenic RAG-1 mutant mice, indicate the existence of a control point at the CD44-CD25+TN stage at which cells expressing a productively rearranged TCR-beta chain are selected for further differentiation.
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PMID:Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiation. 751 23

The analysis of the expression of the alpha chain of the IL-2 receptor (CD25, TAC) on the surface of B lineage cells in mouse bone marrow reveals that it is a useful marker to distinguish pre-B-I from pre-B-II cells. CD25 is not expressed on CD45R(B220)+ c-kit+ CD43+ TdT+ lambda 5+ c mu- sIg-IgH chain locus DJH-rearranged pre-B-I cells of mouse bone marrow. It is expressed on large cycling CD45R(B220)+ c-kit- CD43+ TdT- lambda 5+ c mu+ sIg- and on small resting CD45R(B220)+ c-kit- CD43- TdT- lambda 5- c mu- sIg- IgH chain locus VHDJH-rearranged pre-B-II cells. Therefore, the transition from pre-B-I to large pre-B-II cells is marked by the downregulation of c-kit and terminal deoxynucleotidyl transferase (TdT), and by the upregulation of CD25. SCID, RAG-2T, microMT and lambda 5T mutant mice do have normal, if not elevated numbers of pre-B-I cells but lack all CD25+ pre-B-II cells in their bone marrow. The expression of a transgenic H chain under control of the microH chain enhancer in RAG-2T bone marrow B lineage precursors allows the development of large and small CD25+ pre-B-II cells. The results suggest that the differentiation of pre-B-I to pre-B-II cells in mouse bone marrow requires the expression of microH chains and surrogate L chains in membranes, probably on the surface of precursor B cells.
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PMID:IL-2 receptor alpha chain (CD25, TAC) expression defines a crucial stage in pre-B cell development. 752 94

Ten cell lines recently established from paediatric patients with acute lymphoblastic leukaemia (ALL) were examined for expression of P145c-kit, the growth factor receptor encoded by the c-kit proto-oncogene, by immunofluorescence and flow cytometry using monoclonal antibody YB5.B8. Three of five T-ALL cell lines, but none of five B lineage ALL cell lines displayed significant binding of the antibody. The cell line with the highest level of binding was PER-423 (Kees et al, Leukemia Res 1993; 17: 51-59 which has the phenotype CD7+, CD56bright, CD2-, CD4-, CD5-, CD8-, CD16-, has rearranged T cell receptor beta-chain genes, expresses cytoplasmic CD3 and is strictly dependent on interleukin 2 (IL-2) for proliferation. Recombinant to act in synergy with IL-2 to promote proliferation of PER-423 cells. In five experiments, SLF increased the maximal amount of proliferation by 105 +/- 15%, and decreased the level of IL-2 required for a half-maximal response by 43 +/- 7%. The cells constitutively express the intermediate affinity IL-2 receptor (beta/gamma), but can be induced in the presence of phorbol ester to express the alpha chain (CD25, Tac) which confers high affinity binding of IL-2. In contrast, the alpha chain was not induced by SLF. The enhancement of proliferation of PER-423 cells by SLF could be prevented by inclusion in the assay of a blocking monoclonal antibody to P145c-kit. These experiments demonstrate that SLF/P145c-kit can provide a significant growth stimulus for ALL cells, and PER-423 cells may be a useful system for investigating the mechanism of synergy between SLF and IL-2.
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PMID:Synergistic action of interleukin-2 and Steel factor (SLF) on a human T lymphoblastoid cell line. 754 Oct 97

Chemokines are proinflammatory peptides regulating the functions of various hematopoietic cells. We have analyzed the effects of seven recombinant human (rh) chemokines (MCAF, RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, and IP-10) on the growth and function of human basophils and mast cells. We found that MCAF, but not RANTES, MIP-1 alpha, MIP-1 beta, IL-8, GRO, or IP-10, causes direct and dose-dependent histamine release from basophils (MCAF, 5 micrograms/ml: 26.9 +/- 3.4%; other chemokines: < 5% of total histamine). An increased (2.1 to 3.5-fold) response to MCAF was obtained when basophils were preincubated with rh interleukin-3 (100 units/ml). Moreover, IL-3-primed basophils became responsive to physiologic concentrations (< 1 microgram/ml) of MCAF, IL-8, and RANTES. None of the chemokines tested was able to induce histamine secretion in mast cells obtained from lung (n = 2), skin (n = 1), uterus (n = 3), or tonsils (n = 3), even when cells had been preincubated with the mast cell agonist SCF. The chemokines also failed to modulate the expression of activation antigens (CD11b/C3biR, CD25/IL-2R beta, CD63, IL-3R alpha, CD117/c-kit) on the mast cell line HMC-1 or the basophil cell line KU-812 and were unable to induce differentiation of basophils or mast cells in culture. Together, our results show that basophils respond to rhIL-8, rhMCAF, and rhRANTES and that, unlike human basophils, human mast cells are unresponsive to recombinant chemokines.
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PMID:Differential response of human basophils and mast cells to recombinant chemokines. 754 Dec 56

Differential expression of c-kit, CD25 (TAC), surrogate L chain and cytoplasmic muH chain, and surface expression of IgM and IgD allows the separation of B220 (CD45+) B cell subpopulations. PCR analyses with DNA of single cells developed by others and by us have been used to monitor the conformation of the Ig H and L chain gene loci in these different B lineage subpopulations. The results of these analyses indicate that B220+/c-kit+/CD25- cells are the precursors of large B220+/CD25+/sIgM- which, in turn, are the precursors of small B220+/CD25+/sIgM- cells. The majority of B220+/c-kit+/CD25- cells are DHJH-rearranged, with L chain loci in germline configuration and are thus pre-B I cells. More than 90% of all large B220+/CD25+/sIgM- cells have at least one H chain locus VHDHJH rearranged; half of them have also the second locus VHDHJH rearranged and are thus large pre-B II cells. Rearrangements of at least one allele of the kappa L chain loci become detectable in 65% of the small B220+/CD25+/sIgM- cells, 67% of the immature B and > 75% of the mature B cells. The ratio of kappa L to lambda L gene rearrangements in all three subpopulations is approximately 10:1, indicating that the kappa L/lambda L ratio is established as soon as rearrangements are made.
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PMID:The status of Ig loci rearrangements in single cells from different stages of B cell development. 757 95

Two waves of immunoglobulin gene rearrangements, first of the heavy, then of the light chain chain gene loci form functional immunoglobulin genes during B cell development. In mouse bone marrow the differential surface expression of B220 (CD45R), c-kit, CD25, and surrogate light chain as well as the cell cycle status allows FACS separation of the cells in which these two waves of rearrangements occur. The gene products of two recombination activating genes, RAG1 and RAG2 are crucial for this rearrangement process. Here, we show that the expression of the RAG genes is twice up- and down-regulated, at the transcriptional level for RAG1 and RAG2, and at the postranscriptional level for RAG2 protein. Expression levels are high in D-->JH and VH-->DJH rearranging proB and preB-I cells, low in preB cells expressing the preB cell receptor on the cell surface, and high again in VL-->JL rearranging small preB-II cells. In immature B cells expressing on the cell surface RAG1 and RAG2 mRNA is down-regulated, whereas RAG2 protein levels are maintained. Down-regulation of RAG1 and RAG2 gene expression after productive rearrangement at one heavy chain allele might be part of the mechanisms that prevent further rearrangements at the other allele.
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PMID:Down-regulation of RAG1 and RAG2 gene expression in preB cells after functional immunoglobulin heavy chain rearrangement. 758 50

We have subdivided mouse CD4-CD8-CD3- triple-negative (TN) thymocytes into four subsets based upon expression of CD44 and CD25, including CD44+CD25-, CD44+CD25+, CD44-CD25+ and CD44-CD25-. Characterization of these cells revealed several features distinct to each subset, in particular the expression of high levels of c-kit (the receptor for stem cell factor) by CD44+CD25-TN and CD44+CD25+TN but not by CD44-CD25+TN and CD44-CD25-TN. The CD44+CD25+TN subset also included the IL-7 and stem cell factor-responsive cells, whereas only minimal responsiveness was observed by the CD44- populations. These subsets also showed differential cytokine production potential (CD44+CD25- > CD44+CD25+ > CD44-CD25+ > CD44-CD25-) after stimulation with calcium ionophore, PMA and IL-1. The repopulation potential of these subsets in 2-deoxyguanosine-treated fetal thymic lobes supports the following maturation sequence: CD44+CD25- -->CD44+CD25+ -->CD44-CD25+ -->CD44-CD25-. Furthermore, the sequence of progression from CD44+CD25+ to CD44-CD25+ cells was confirmed by their TCR beta-chain gene configuration. The former population exhibits germ-line TCR beta-chain configuration, whereas the latter subset shows a rearranged pattern.
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PMID:A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8- triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. 838 91

Transgenic mice in which mouse interleukin (IL)-7 cDNA is expressed under the control of the mouse major histocompatibility complex (MHC) class II (E alpha) promoter develop a lymphoproliferative disease characterized by the early polyclonal expansion of T cells followed in many cases by the development of lymphomas of immature B cells. Here, we have analyzed B cell development in these transgenic mice. Phenotypic analysis using monoclonal antibodies to B220, IgM, IgD, c-kit, IL-7 receptor, MHC class II, AA4.1, CD19, CD23, CD25, CD40 and CD43 shows that B lymphopoiesis in the bone marrow is dramatically altered and the number of pro/pre-B and immature B cells is significantly increased. Interestingly, pro/pre-B and immature B cells persist in the spleens of adult transgenic mice and are also present in lymph nodes and blood. Cell cycle analysis of lymph node cells shows that subpopulations of developing B cells retain the cell cycle profiles of their bone marrow counterparts. Limiting dilution analysis shows that the number of clonable pre-B cells is significantly increased and that at limiting dilution, growth of transgenic pre-B cells is still dependent on exogenous IL-7. Using semiquantitative polymerase chain reaction (PCR) and in situ hybridization, the level of IL-7 transcripts in the spleen was found to decrease between 2 and 4 weeks in control mice with levels in transgenics mice being approximately 50 times greater. These transgenic mice represent an interesting model with which to study the effects of IL-7 overexpression in the bone marrow and raise interesting questions regarding the regulation of B lymphopoiesis in normal mice.
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PMID:Phenotypic and functional analysis of B lymphopoiesis in interleukin-7-transgenic mice: expansion of pro/pre-B cell number and persistence of B lymphocyte development in lymph nodes and spleen. 856 80

B cell development in RAG-2-deficient (RAG-2T) mice is impeded at an early stage, due to the inability of these animals to rearrange their endogenous ig gene loci. Expression of an E mu-bcl-2 transgene in these mice did not change this phenotype. However, stromal cell/IL-7-reactive B cell progenitors (pro-B cells) were found in fetal live and bone marrow of RAG-2T and RAG-2T/E mu-bcl-2 transgenic mice in numbers comparable to normal mice. Like cells from normal mice they are c-kit+, surrogate L chain+ and CD25-, and can proliferate in vitro for long periods of time. Upon IL-7 deprivation, they can be induced to differentiate into c-kit-, surrogate L chain- and CD25+ cells that are no longer clonable on stromal cells and IL-7. Furthermore, sterile transcription from the kappa L chain gene loci is induced. The latter was also observed with pro-B cells directly isolated ex vivo from the bone marrow of RAG-2-deficient animals. The results suggest that progenitor B cell differentiation can occur in cells from V(D)J recombinase-deficient mice to the stage where kL chain gene rearrangements would normally be initiated. It further indicates that some molecular programs of early B cell differentiation can take place in the absence of Ig gene rearrangements.
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PMID:Induction of sterile transcription from the kappa L chain gene locus in V(D)J recombinase-deficient progenitor B cells. 874 61

Human bone marrow stromal cell antigen 1 (BST-1) was identified as a glycosylphosphatidyl-inositol-anchored ectoenzyme expressed on bone marrow stromal or synovial cell lines and having the ability to facilitate pre-B cell line growth. The analysis of the expression of mouse BST-1/BP-3 on the surface of lymphoid cells in the bone marrow and thymus revealed that it was very transiently expressed on both B and T cell progenitors undergoing gene rearrangement of the antigen receptor. Among CD45R+ CD43+ B cell progenitors in the bone marrow, BST-1 expression appeared on the CD24 (heat stable antigen)+, CD19+ or CD117 (c-kit)+ population. In the thymus, BST-1 was expressed on CD4-CD8-CD3- [triple negative (TN)] CD90 (Thy-1)+ cells. In TN thymocytes, the majority of CD25+ cells and CD44(10)/- cells expressed BST-1. In fetuses, BST-1+ cells appeared in the thymus and liver at day 14 and 16 of gestation respectively. The expression level of BST-1 by fetal thymus was maximal and > 60% of thymocytes were positive for BST-1 at day 15 or 16 and the proportion then gradually decreased during development. Among day 15 fetal thymocytes, BST-1 was negative on the CD44+ CD25- fraction, very slightly positive on the CD44+ CD25+ fraction, and strongly positive on the CD44(10)/- CD25+ and CD44-CD25- fractions. These results showed that murine BST-1 is a useful marker for lymphoid progenitor cells initiating gene rearrangement of their antigen receptors.
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PMID:Stage-specific expression of mouse BST-1/BP-3 on the early B and T cell progenitors prior to gene rearrangement of antigen receptor. 892 17


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