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

We describe here the development and characterization of the FLS4.1 stromal line derived from 15-day fetal liver of BALB/c embryos and defined culture conditions that efficiently support the cloning and long-term growth of nontransformed B-220+ 14-day fetal liver cells at two stages of B-cell development, namely, pro-B lymphocytes (immunoglobulin [Ig] genes in germ line configuration) and pre-B cells (JH-rearranged genes with both light-chain Ig genes in the germ line state). All B-cell precursor clones require recombinant interleukin-7 (rIL-7) and FLS4.1 stromal cells for continuous growth in culture, but pro-B lymphocyte clones can also proliferate in rIL-3. None proliferate in rIL-1, rIL-2, rIL-4, rIL-5, rIL-6, or leukemia inhibitory factor. FLS4.1 stromal cells synthesize mRNA for Steel factor but not for IL-1 to IL-7; all pro-B and pre-B clones express c-Kit, the receptor for Steel factor, and a c-Kit-specific antibody inhibits the enhanced proliferative response of fetal liver B-220+ B-cell precursors supported by FLS4.1 stromal cells and exogenous rIL-7 but does not affect that promoted by rIL-7 alone. Northern (RNA) blot analysis of the expression of the MB-1, lambda 5, Vpre-B, c mu, RAG-1, and RAG-2 genes in pro-B and pre-B clones show that transcription of the MB-1 gene precedes IgH gene rearrangement and RNA synthesis from c mu, RAG-1, RAG-2, lambda 5, and Vpre-B genes. All clones at the pre-B-cell stage synthesize mRNA for c mu, RAG-1, and RAG-2 genes; transcription of the lambda 5 and Vpre-B genes seems to start after D-to-JH rearrangement in B-cell precursors, indicating that the proteins encoded by either gene are not required for B-cell progenitors to undergo D-to-JH gene rearrangement. These findings mark transcription of the MB-1 gene as one of the earliest molecular events in commitment to develop along the B-lymphocyte pathway. Indeed, both pro-B and pre-B clones can generate in vitro and in vivo B lymphocytes but not T lymphocytes; moreover, these clones do not express the CD3-gamma T-cell-specific gene, nor do they have rearranged gamma, delta, or beta T-cell antigen receptor genes.
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PMID:Fetal liver pro-B and pre-B lymphocyte clones: expression of lymphoid-specific genes, surface markers, growth requirements, colonization of the bone marrow, and generation of B lymphocytes in vivo and in vitro. 134 35

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

CD34, a stem cell marker, has been shown to be expressed on human CD3-CD4-CD8- (triple-negative; TN) thymocytes. Phenotypic and functional analyses suggest the following differentiation sequence: CD34+1-3-4-8(-)--> CD34+1+3-4 +/- 8(-)-->CD34-1+3-4+8(+/-)-->CD34-1++3-4+8+. In this report, we examined cytokine receptor gene expression on these subsets by reverse transcription-polymerase chain reaction analysis (RT-PCR). We were able to detect interleukin-7 receptor (IL-7R), c-kit and IL-2R gamma in all CD34+ thymocyte subsets, consistent with previous functional studies. We found IL-1R, granulocyte/macrophage colony-stimulating factor receptor-alpha and IL-4R transcripts in CD3- and CD34+ subsets. Secondly, we investigated T cell receptor (TCR)-delta and -beta gene rearrangement and transcription in CD34+ thymocytes. Our results show that a full-length TCR-delta transcript and the recombination activating genes RAG-1 and RAG-2 mRNA were already expressed in the CD34+1- subset. Mature V beta-containing TCR transcripts were also detected in the CD34+1+ subset, but not in the CD1- fraction. Furthermore, PCR analysis of D-J beta gene rearrangements showed that > or = 70% of CD34+1- cells are in a TCR beta germ-line configuration, although D-J beta recombination had already started in this population.
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PMID:CD34-positive early human thymocytes: T cell receptor and cytokine receptor gene expression. 758 13

Proteins expressed from productively rearranged H and L chain gene loci have been implied in the regulation of Ig gene rearrangements during B lymphopoiesis. However, recent findings suggest that early B cell development can occur without expression of surrogate L chain, without deposition of microH chains into membranes, without productive H chain gene rearrangements, and even without any rearrangements of Ig gene loci. In bone marrow, 2-5% of all B220-, sIgM-, c-kit+ cells are pro B cells that undergo differentiation from B220- via B220+, c-kit+, CD43+, clonable long-term proliferating pre B-I cells to B220+, c-kit-, CD43-, IL-2 receptor+ pre B-II cells and immature B cells, only to die by apoptosis in situ within less than 4 days. A membrane-bound complex of surrogate H chain (gp130/gp35-65) and surrogate L chain expressed on pro B and pre B-I cells has apparently no influence on this early development. Pre B-I cells carrying DHJH-rearrangements in reading frame (rf) II are counter-selected, probably because they can express an Ig-like complex of truncated DHJHC mu-protein and surrogate L chain, while pre B-I cells DHJH-rearranged in rf I or III are not suppressed. Immature sIg+ B cells, also from bcl-2 transgenic mice, can continue to rearrange L chain gene loci. Thus, mere membrane deposition of Ig, even with concomitant expression of bcl-2, terminates neither expression of RAG-1 and 2, nor secondary L chain gene rearrangements, nor does it allow the development of mature B cells. Membrane-bound expression of an Ig-like complex of microH chains and surrogate L chains appears to be needed to generate the 50-70 million pre B-II cells in bone marrow. However, the membrane-bound expression of Ig is mandatory for negative and positive selection of immature B cells. Autoantigens delete or anergize self-reactive B cells. We speculate that all mature, resting, primary antigen-reactive B cells in the periphery have been selected from immature sIg+ B cells by unknown antigens and have, thereby, changed their lifestyle from rapid death by apoptosis to longevity.
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PMID:Roles of IgH and L chains and of surrogate H and L chains in the development of cells of the B lymphocyte lineage. 801 Dec 81

The SL/Kh strain of mice spontaneously develop two types of non-thymic lymphomas at a high incidence and very short latency. The major type of lymphomas induce systemic lymph node enlargement and hepatosplenomegaly, and the minor type, proliferation predominantly in bone marrow often associated with spinal paralysis. Phenotypes of both types of lymphomas are indistinguishable: they express B220, 6C3, c-kit but not Thy-1.1, Mac-1 and surface Ig. In both types of lymphomas, the immunoglobulin heavy chain gene is found clonally rearranged in the order of VH-D-JH, whereas the light chain gene remains in germ line configuration. About half of the primary lymphomas are dual or oligoclonal in origin. R-PCR also demonstrates expression of lambda 5, RAG-1 and RAG-2, which are specifically associated with pre-B stage lymphocytes. All these observations indicate that both types of the SL/Kh lymphomas are pre-B-lymphomas.
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PMID:SL/KH strain of mice: a model of spontaneous pre-B-lymphomas. 832 39

We have revealed that about one and a half thousand tiny clusters, filled with one thousand closely packed lymphocytes, can be found throughout the murine small and large intestinal mucosa. They are located in crypt lamina propria (cryptopatches; CP) and can be first detected at 14-17 d after birth. A large fraction of lymphocytes in CP expresses c-kit, IL-7R, Thy1 and a lymphocyte function-associated antigen, LFA-1, whereas most of them remain CD3-, TCR alpha beta-, TCR gamma delta-, sIgM-, and B220-. The population size of IL-2R alpha+, HSA+ and Pgp-1+ subsets is variable (20-50%) and the composition of CD8+, Ly-1+, and CD4+ subsets is smaller but also variable (3-20%). In the small intestine, CP do not contain cells undergoing apoptosis nor cells bearing RAG-1 molecules, but do contain dendritic stromal cells bearing CD11c/CD18 molecules. The frequency of DNA replicating cells in CP is higher than that in Peyer's patches (PP), is lower than that in the thymic cortex and is almost comparable with that in the thymic medulla. The numbers of CP remain the same in aged mice (> 114 wk) but double after estrogen treatment even though the thymi are attenuated sharply in both conditions. Thus, with respect to histogenesis, lymphocyte composition and tissue level of cellular behavior, neither PP, isolated lymphoid follicles, peripheral LNs, nor thymus are identical with CP. Finally, CP are virtually absent in lamina propria of IL-7R-deficient mice that display a profound reduction in thymic and peripheral lymphoid cellularity. By contrast, CP are present in germ-free mice and in athymic (nu/nu), SCID, TCR beta x delta-/-, RAG-2-/-, PP-deficient (aly/aly), stem cell factor (Sl/Sld) and c-kit (W/Wv) mutant mice. Taking all of these results together, CP are the first identification of gut-associated murine lymphoid tissues where the generation of IL-7-dependent lympho-hematopoietic progenitors for T and/or B cell descendants may start to take place at the age of commencement of weaning.
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PMID:Identification of novel lymphoid tissues in murine intestinal mucosa where clusters of c-kit+ IL-7R+ Thy1+ lympho-hemopoietic progenitors develop. 887 90

Relatively little is known about the relationship of lymphoid-associated gene expression to the proliferation and differentiation potential of early human bone marrow lymphoid progenitors. Surface expression of interleukin-7 (IL-7) receptor-alpha (IL-7R alpha), a component of the high-affinity receptor for the lymphoid precursor growth factor IL-7, defined a CD34+ progenitor subset lacking the CD19+ pro-B phenotype but demonstrating markedly enhanced lymphoid clonogenic capacity and the ability to differentiate into pro-B cells in short-term culture. These progenitors expressed mRNA for the lymphoid-associated genes Ig beta, RAG-1, and PAX-5, and were uniformly TdT-positive (TdT+). In contrast, IL-7R alpha-/CD19-/ CD34+ progenitors had a 50-fold reduced lymphoid clonogenic capacity and did not differentiate into pro-B cells in short-term culture. Expression of TdT and the lymphoid-associated genes Ig beta and RAG-1, but not PAX-5, was detected in this fraction, although at lower levels than in the IL-7R alpha+ progenitors. In contrast to IL-7R alpha, loss of the stem cell factor receptor c-kit was associated with enhanced lymphoid clonogenic potential and increased B-lineage differentiation potential. These results indicate that IL-7R alpha expression defines entry into a developmental stage characterized by upregulation of multiple lymphoid-associated genes and enhanced fitness for B-lymphoid differentiation. The onset of IL-7R alpha and PAX-5 expression immediately before acquisition of CD19 is consistent with evidence suggesting upregulation of CD19 through pathways involving PAX-5 and IL-7.
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PMID:Expression of interleukin-7 receptor by lineage-negative human bone marrow progenitors with enhanced lymphoid proliferative potential and B-lineage differentiation capacity. 902 24

Hemopoiesis, initiated in the early embryo yolk sac (YS) (7.5-8 days postcoitum (pc) in mouse), takes place thereafter in sites successively seeded by extrinsic hemopoietic stem cells (HSC). Since the existence of intraembryonic HSC has been proven experimentally in some vertebrates, it is also likely that not all HSC originate in the YS in mammals, as previously thought. Candidate intraembryonic sites that may be active in producing HSC before liver colonization are the para-aortic splanchnopleura (P-Sp) and the aorta-gonads-mesonephros region (AGM). Here we explore these sites directly for the presence of cells with hemopoietic-specific surface molecules and gene activities. The Ags c-kit, AA4.1, Mac-1, and Sca-1 begin to be expressed on some P-Sp and AGM cells, making it possible to distinguish subpopulations that evolve according to reproducible developmental patterns. On the basis of RAG-1 gene transcription, the first lymphoid precursors in the mouse embryo appear to be present 9.5 to 10 days pc in P-Sp/AGM and YS. Starting B-cell lymphopoiesis (9-12 days pc) is characterized by nonexpression of the surrogate light chain lambda 5-encoding gene and biased usage of IgH DJ4 rearrangements. In the 12.5- to 13.5-day-pc fetal liver (FL), a switch occurs, characterized by the random use of all IgH DJ and the detection of lambda 5 gene transcripts.
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PMID:Antigenic phenotype and gene expression pattern of lymphohemopoietic progenitors during early mouse ontogeny. 905 95

We hypothesize that early lymphoid commitment from primitive hematopoietic marrow progenitors is governed by signals from the marrow microenvironment leading to sequential induction of lineage-specific genes. Using expression of lymphoid genes as markers of differentiation, we characterize a highly purified population (>99.8% by double sorting) of primary human CD34+Lin-DR- progenitors. This population was then used to evaluate the effects of supplemental cytokines (interleukin-2 [IL-2], IL-3, IL-7, c-kit ligand), FLT-3 ligand (FL), and stroma-derived factors on lymphoid differentiation in vitro. CD3, RAG-1, Ikaros, CD10, and TdT transcripts were detected in the starting CD34+Lin-DR- population. By contrast, CD3gamma, CD3delta, CD3zeta, and RAG-2 transcripts were not present in any samples tested. The presence of supplemental cytokines alone at culture initiation permitted stimulation of the expression of CD3zeta, but not of CD3gamma or CD3delta. However, when FL and stroma-derived factors were added to cytokines, CD3 gene expression was induced in all samples. The predominant CD3 transcripts induced by optimal culture conditions were alternatively spliced isoforms lacking transmembrane sequences (CD3delta and CD3gamma) and portions of the intracellular and extracellular domains (CD3gamma). The combination of cytokines, FL, and stromal factors also provided a potent stimulus for RAG-2 gene expression. These findings show that FL in combination with stroma-derived factors provide important signals to promote early events required for lymphoid differentiation.
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PMID:FLT-3 ligand and marrow stroma-derived factors promote CD3gamma, CD3delta, CD3zeta, and RAG-2 gene expression in primary human CD34+LIN-DR- marrow progenitors. 947 32

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and estrogen induce thymic atrophy and alter thymocyte development. In the present study we investigate whether TCDD and the synthetic estrogen diethylstilbestrol (DES) alter intrathymic development by the same or different mechanisms. We compared the effects of TCDD and DES on thymocyte development in fetal thymus organ culture (FTOC) and found that both compounds caused a reduction in cell yield. TCDD- and DES-treated FTOCs yielded fewer CD4 + CD8+ double-positive cells. However TCDD treatment also led to a greater percentage of cells in the CD8+ single-positive compartment. At lower dioxin concentrations, our results demonstrated an actual increase in CD8+ cells, whereas DES-treated fetal thymocytes were mainly enriched in CD4-CD8- double-negative cells. More alpha beta-TCR+ positive cells were seen in TCDD- but not in DES-exposed cultures. Furthermore, in this study we found that TCDD and DES also alter intrathymic development at different stages in the CD4-CD8- double-negative compartment. TCDD induced a relative increase in c-kit + CD44 + CD25-HSA-thymocytes, while DES induced an relative increase in c-kit-CD44-CD25 + HSA+ cells. RT-PCR revealed that TCDD reduced RAG-1, RAG-2, and TdT gene expression in the CD4-CD8- double-negative thymocytes. Co-treatment by TCDD and DES in FTOC yielded a mixture of effects induced by each agent. Taken together, our results demonstrate that TCDD and DES affect thymocytes at different stages of development, suggesting distinct mechanisms for induction of thymic atrophy.
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PMID:2,3,7,8-Tetrachlorodibenzo-p-dioxin and diethylstilbestrol affect thymocytes at different stages of development in fetal thymus organ culture. 957 85


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