Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10721 (c-kit)
 6,575 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human mast cells have been purified from uterine tissues, and their surface marker profile and function have been evaluated as part of ongoing studies of mast cell heterogeneity. Using a panel of antibodies, purified uterine mast cells (UMC; 81% +/- 7% purity, n = 10) were analyzed by immunofluorescence and flow cytometry for surface expression of various antigens. Consistent with previous analyses of mast cells from other tissues, UMC expressed HLA class I, IgE, c-kit receptor, CD9, CD33, CD43, CD45, and CD54, while CD11a, CD11b, CD14, CD16, CD23, and CD64 were not detected. Unlike other mast cells, UMC expressed CD11c/CD18 (p150,95) and CD32 (Fc gamma RII). Additional antigens not previously studied on mast cells included the selectin LECAM-1 (Leu-8) and several beta 1 and beta 3 integrins; expression of very late activation antigen-4 (VLA-4) (CD49d/CD29), VLA-5 (CD49e/CD29), and the vitronectin receptor (CD51/CD61) was seen. Functional studies showed that treatment of human umbilical vein endothelial cells with interleukin-1 (5 ng/mL for 4 hours) resulted in a twofold to threefold increase in adhesiveness for UMC. Purification procedures did not alter histamine release responses to anti-IgE or the calcium ionophore A23187, and treatment of UMC with an anti-CD32 monoclonal antibody (IV.3) did not induce histamine release or alter anti-IgE-induced release. These data suggest that UMC may possess unique phenotypic characteristics, and support the concept of mast cell heterogeneity.
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PMID:Immunophenotyping and functional analysis of purified human uterine mast cells. 137 Jun 42

To understand regulation of hemopoiesis, it would be helpful to identify physiologically relevant function-associated molecules on stem cells. Here, we report the detailed examination of CD43 expression on murine and human pluripotent hemopoietic stem cells. Mouse stem cells were found within the Ly6+Lin-CD43high subpopulation of bone marrow. These cells, upon transfer into SCID mice, caused rapid repopulation of thymus, spleen, and bone marrow. Retransfer of bone marrow cells from primary SCID recipients of Ly6+Lin-CD43high cells into secondary recipients resulted in repopulation of lymphohemopoietic cells. All Ly6+Lin-CD43high cells were found to express high levels of c-kit. In contrast, Ly6+Lin-CD43-/low cells caused limited and variable thymic and splenic repopulation. These cells failed to repopulate the marrow cavity and did not contain retransplantable stem cells. These data indicate that murine pluripotent stem cells express high levels of CD43. Examination of human fetal bone marrow cells revealed a population of CD34+CD38-CD43+ cells. When single sorted cells with this phenotype were cultured in vitro, they were able to produce colonies with a dispersed growth pattern. Cells with this growth pattern have previously been shown to have myeloid and lymphoid growth potentials and extensive self-renewal capacity. Furthermore, CD34+CD38-HLA-DR+ cells, recently shown to be highly enriched in stem cell activity, expressed relatively high levels of CD43. Because CD43 has recently been shown to bind to intercellular adhesion molecule-1, these data suggest a possible role for CD43 in the regulation of hemopoiesis.
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PMID:Expression of CD43 on murine and human pluripotent hematopoietic stem cells. 752 20

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

Clones and lines of precursor (pre) B cells can be established by limiting dilutions of unseparated cell suspensions of fetal liver or bone marrow on stromal cells in the presence of interleukin (IL)-7. When IL-3 is used instead of IL-7, cultures are regularly overgrown by different precursor cells of the myeloid lineage, as well as by adherent cells that inhibit pre-B-cell expansion. However, in the presence of either IL-7 or IL-3, clones of pre-B cells can be established on stroma cells at frequencies near one in one when the cultures are initiated with cell sorter purified CD45RO (B220)+/c-kit+ fetal liver or bone marrow derived pre-B cells. Clones grown on stromal cells in the presence of IL-7 can be regrown in IL-3, and vice versa. Pre-B cells that proliferate on stromal cells in the presence of IL-7 or IL-3 have the same phenotype, ie, are B220+ c-kit+, CD43+, and surrogate light chain+. Removal of the growth factors (IL-7, respectively IL-3) from the cultures results in differentiation to surface immunoglobulin (slg) positive, c-kit-, CD43-, surrogate light chain- B cells, a fraction of which is lipopolysaccharide (LPS) responsive as shown by IgM secretion. These results show that IL-7 and IL-3 stimulate largely overlapping populations of precursor B cells from bone marrow to proliferate for long periods of time in the presence of stromal cells. Thus, IL-7 and IL-3 are alternative growth factors for the same pre-BI cell.
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PMID:Interleukin-3 and interleukin-7 are alternative growth factors for the same B-cell precursors in the mouse. 753 88

Progenitor and precursor B lymphocytes with the capacity of long-term proliferation on stromal cells in the presence of interleukin-7 (IL-7) can be cloned ex vivo from fetal liver, neonatal blood, and spleen, and from adult bone marrow (BM) in frequencies that are similar in different strains of mice and that change with age. A wave of clonable cells appears before birth and disappears after birth in liver. Up to 2 weeks after birth, high frequencies of clonable cells are present in spleen but become undetectable at 6 to 8 weeks of age. In BM, high frequencies (1 in 50) of clonable cells are present early after birth, and then decrease continuously to 10- to 20-fold lower levels at 6 to 8 months of age. The earliest clonable cells have at least part of their IgH genes in germline configuration. Clones of pro/pre B cells apparently continue to rearrange DH to JH segments on both chromosomes. Rearrangements without insertion of N-sequences at the DHJH joints are found in fetal liver, while DHJH joints in pre B cells of spleen and BM throughout life have N-regions inserted. At least half of all primary pre B-cell clones develop mitogen-reactive B cells after differentiation to sIg+ B cells. Clonable pro and pre B cells are enriched in B220- c-kit(low) as well as in B220+ c-kit+ and B220+ CD43+ cell populations of BM. The frequencies of clonable cells in the B220- c-kit(low) BM cell population decrease 10- to 20-fold during 8 months of life, while those in the B220+ c-kit+ population remain constant, although their absolute numbers drop 5- to 10-fold during that time. All long-term proliferating clones express the surrogate L chain VpreB/lambda 5 as well as c-kit and CD43 on all cells. The number of total clonable pro and pre B cells is at best 10% of the number of cells required to produce the estimated daily output of 5 x 10(7) B-lineage cells in a mouse. This suggests that the production of a relatively constant number of B cells during adulthood may be effected by precursors, which are not clonable on stromal cells and IL-7 with long-term proliferative capacity. On the other hand, BM transplantation experiments indicate that a mouse retains B220- progenitors throughout life, from which pre B and B cells can be generated in old mice in frequencies characteristic of young mice.
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PMID:Changes in frequencies of clonable pre B cells during life in different lymphoid organs of mice. 768 15

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 kinetics of kappa light (kappa L) chain gene rearrangement and expression on mRNA and protein level has been studied with four stromal cell/IL-7 reactive, long-term in vitro proliferating pre-B cell lines and clones, two from fetal liver of normal mice and two from fetal liver of E microH-bcl-2 transgenic (bcl-2-tg) mice. These pre-B cell lines and clones are DJH-rearranged on both H chain alleles. Two of the clones harbor H chain rearrangements which do not allow the expression of VHDJH rearranged H chain genes as microH chain proteins. Upon removal of IL-7 from the pre-B cell cultures all four cell lines rearrange VH-DJH and VL-JL gene segments, loose the surface expression of c-kit, CD43, and surrogate light chain, as well as the capacity to be clonable on stromal cells in the presence of IL-7. Pre-B cells from normal mice die by apoptosis during differentiation, while those from bcl-2-tg mice do not. All four lines and clones express comparable levels of mRNA for microH and kappa L chains with the same time kinetics during 3 days of differentiation. However, only two of the four pre-B cell lines and clones express microH chain protein, whereas all four pre-B cell lines and clones express kappa L chain protein at comparable levels between 2 x 10(5) and 1.4 x 10(6) kappa L chain molecules per cell. These results suggest that microH chain expression is not mandatory for rearrangement and normal expression of kappa L chain genes when pre-B cells differentiate to B cells.
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PMID:Rearrangement and expression of kappa light chain genes can occur without mu heavy chain expression during differentiation of pre-B cells. 831 30

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

Previous studies have shown that stem cells able to competitively reconstitute the hematopoietic system of lethally irradiated mice (competitive repopulating units [CRU]) can be obtained in highly purified form from adult mouse bone marrow (BM) by the isolation of cells with a Sca-1+Lin-WGA+ phenotype. We now report on the phenotypic characteristics of CRU from day-14.5 murine fetal liver (FL). Our results confirm previous reports of similarities between the two CRU populations but also reveal a few striking differences. Both were found to express the Sca-1 antigen (SCA-1+ and surface molecules that bind wheat germ agglutinin (WGA+), and both show an absence or low expression of a number of markers characteristic of mature hematopoietic cells: B220, Gr-1,ly-1 and Ter119 (together termed Lin*-). Limiting dilution analysis of recipients transplanted with purified Sca-1+Lin*- FL cells with intermediate forward- and side-scatter properties showed that the frequency of CRU in this FL subpopulation was one in 39 cells. This represents an enrichment of approximately 450-fold over the labeled but unseparated FL starting population (one in 17,300 total FL cells). These FL CRU also resembled their counterparts in adult BM in that they expressed high levels of MHC class I and CD43 and intermediate levels of heat-stable antigen (HSA) and c-kit and did not express, or expressed at a low level, Thy-1.2, CD71, and the antigen recognized by the Fall-3 monoclonal antibody (mAb). In contrast, a high percentage of the Sca-1+Lin*- cells isolated from 14.5-day-old FL stained with the AA4.1, anti-Mac-1, and the anti-CD45RB mAbs and retained Rhodamine 123 (Rh123(bright)), whereas the Sca-1+Lin-WGA+ CRU-containing fraction of adult BM cells was found to be AA4.1-, Mac-1-, CD45RB-, and Rh123(dull). These differences in phenotype between CRU in FL and adult BM indicate changes that occur during ontogeny in cells that are similar with respect to their totipotentiality and long-term repopulating potential and complement parallel observations of functional differences between these two populations of CRU.
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PMID:A comparison of long-term repopulating hematopoietic stem cells in fetal liver and adult bone marrow from the mouse. 860 69

Multiple cytokines can synergize to stimulate the in vitro proliferation and exclusive myeloid differentiation of multipotent bone marrow progenitor cells. The ligand for c-kit (stem cell factor [SCF]) plays a key role in stimulating myeloid and erythroid cell production of primitive hematopoietic progenitors. SCF in combination with interleukin-7 (IL-7) can also stimulate the combined myeloid and B-cell differentiation of uncommitted hematopoietic progenitor cells as well as the growth of early B-cell progenitor cells, although the involvement of c-kit in early B lymphopoiesis remains controversial. In the present study, the flt3-ligand (FL), which, in combination with other cytokines, has overlapping activities with SCF on myeloid cell production from uncommitted progenitors, was investigated for its ability to induce selective stroma-independent B-cell commitment from uncommitted Lin-Sca-1+ bone marrow progenitor cells. IL-7 alone did not induce any clonal growth and FL alone gave rise to a few clusters (< 50 cells) but no colonies (> 50 cells), whereas the combined stimulation with FL and IL-7 resulted in clonal growth of 10% of Lin-Sca-1+ bone marrow cells. After 12 days of incubation of Lin-Sca-1+ cells in FL + IL-7, an almost 400-fold increase in cell production was observed. Phenotyping showed that greater than 99% of the cells produced were of the B-cell lineage, in that they expressed B220, but not cell surface markers specific for myeloid, erythroid, or T-cell lineages. Furthermore, the cells did not express cytoplasmic mu-heavy chain (cmu) or surface IgM, but were positive for CD24 (heat stable antigen [HSA]) and CD43 (leukosialin), suggesting that the cells produced were blocked at a late pro-B-cell stage. Interestingly, although all FL + IL-7-responsive Lin-Sca-1+ progenitor cells and the resulting pro-B cells expressed c-kit, FL + IL-7 was much more potent (62-fold) than SCF + IL-7 in stimulating production of cells of the B-cell lineage. In addition, whereas FL + IL-7 selectively stimulated the production of pro-B cells, SCF + IL-7 predominantly stimulated the production of mature granulocytes. Replating studies showed that FL + IL-7-responsive Lin-Sca-1+ progenitors were not committed to the B-cell lineage, because after 2 days of incubation in FL + IL-7, 80% of the progenitors retained a myeloid potential. As much as 27% of the FL + IL-7-responsive progenitors remained uncommitted after 7 days of incubation, but all had committed to the B-cell lineage after 10 days of incubation in FL + IL-7. These results show that FL much more potently and selectively than SCF synergizes with IL-7 to enhance B-cell commitment and development from uncommitted progenitor cells.
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PMID:Combined signaling through interleukin-7 receptors and flt3 but not c-kit potently and selectively promotes B-cell commitment and differentiation from uncommitted murine bone marrow progenitor cells. 869 43


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