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Results for “Immunologic Capping”

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At least 433 records · Page 24Linked to original sources
PubMed1998

Wiskott-Aldrich syndrome protein-deficient mice reveal a role for WASP in T but not B cell activation.

The Wiskott-Aldrich syndrome (WAS) is a human X-linked immunodeficiency resulting from mutations in a gene (WASP) encoding a cytoplasmic protein implicated in regulating the actin cytoskeleton. To elucidate WASP function, we disrupted the WASP gene in mice by gene-targeted mutation. WASP-deficient mice showed apparently normal lymphocyte development, normal serum immunoglobulin levels, and the capacity to respond to both T-dependent and T-independent type II antigens. However, these mice did have decreased peripheral blood lymphocyte and platelet numbers and developed chronic colitis. Moreover, purified WASP-deficient T cells showed markedly impaired proliferation and antigen receptor cap formation in response to anti-CD3epsilon stimulation. Yet, purified WASP-deficient B cells showed normal responses to anti-Ig stimulation. We discuss the implications of our findings regarding WASP function in receptor signaling and cytoskeletal reorganization in T and B cells and compare the effects of WASP deficiency in mice and humans.

Animals↗
PubMed1983

T cell hybrids that express a VH idiotope-related determinant on a glycoprotein distinct from H-2, Thy-1, and Lyt-1 molecules.

Two mouse monoclonal antibodies to chicken immunoglobulin VH-associated idiotypes (Id), CId-1 and CId-2, were used as probes for Id determinants on mouse T cells. CId-1, which recognized chicken antibodies to N-acetyl glucosamine (NAGA), and approximately 0.4% of chicken T lymphocytes also reacted with approximately 0.2% of BALB/c splenic Thy-1.2+ cells. When enriched CId-1+ splenic T cells from NAGA-immune BALB/c mice were fused with the AKR thymoma BW 5147 cell line, 2 of 72 resulting hybrids, termed CId-1A and CId-1B, were reactive by indirect immunofluorescence with the CId-1 antibody. CId-1 determinants were expressed both in the cytoplasm and on the cell surface. Immunofluorescence studies revealed that both CId-1+ T cell hybrids were phenotypically identical: CId-2-/Ig-/Lyt-1+2-/Thy-1.2+/II-2d+/I-Ad-/I-Ak-/I-Jd+/I-Jk+. Incubation of CId-1B hybrid cells with concanavalin A or lentil lectin resulted in capping of the CId-1 determinant, whereas incubation with pokeweed mitogen, lipopolysaccharide, phytohemagglutinin, and wheat germ agglutinin had no effect on the cell surface distribution of the CId-1 molecule. Trypsin or pronase treatment resulted in the loss of detectable CId-1 determinant on the cell surface. Treatment of CId-1B cells with tunicamycin also reduced the immunofluorescence intensity of the surface CId-1 determinant, but had no effect on its cytoplasmic expression. CId-1 antibody-induced capping of the CId-1 marker did not affect the surface distribution of Lyt-1, Thy-1.2, H-2d, I-Jd, or I-Jk molecules. Conversely, capping of I-Jd and I-Jk determinants did not alter the surface distribution of CId-1. These results suggest that the CId-1 determinant is on a glycoprotein that is not physically linked to the Lyt-1, Thy-1.2, H-2d, I-Jd, and I-Jk molecules. The clonal restriction of CId-1 expression by T cells suggests that the CId-1+ molecule could be a T cell antigen receptor.

Animals↗
PubMed1979

The effects of pharmacologic agents on immune-complex-induced redistribution of B-lymphocyte Fc receptors.

The effects of pharmacologic agents on the immune-complex-induced redistribution of B-lymphocyte Fc receptors (and, as a control, the anti-Ig induced redistribution of surface Ig) were examined. Immune-complex-induced capping of B-cell Fc receptors was moderately to markedly inhibited by the combination of colchicine and cytochalasin B, the Ca++ ionophore A23187, and the local anaesthetic lidocaine but was only slightly inhibited by cytochalasin B alone and was not inhibited by colchicine alone. Inhibition of capping was not due to the inhibition of binding of immune complexes to the B-lymphocytes or to decreased cell viability since these effects were absent. Preformed immune complex-Fc receptor caps were disrupted by A23187, lidocaine, and the combination of colchicine and cytochalasin B, but not by either colchicine or cytochalasin B alone. The effects of the pharmacologic agents were similar for Fc receptors and surface Ig in all cases. These results suggest that ligand bound Fc receptors are affected by cytoskeletal structures and that the ligand-induced redistribution of two distinct B lymphocyte surface receptors (fc receptors and surface Ig) occurs by similar or identical mechanisms.

Animals↗
PubMed1978

Transmembrane interactions and the mechanisms of transport of proteins across membranes.

We have made observations, by double fluorescence staining of the same cell, of the distributions of surface receptors, and of intracellular actin and myosin, on cultured normal fibroblasts and other flat cells, and on lymphocytes and other rounded cells. The binding of multivalent ligands (a lectin or specific antibodies) to a cell surface receptor on flat cells clusters the cell receptors into small patches, which line up directly over the actin- and myosin-containing stress fibers inside the cell. Similar ligands binding to rounded cells can cause their surface receptors to be collected into caps on the surface, and these caps are invariably found to be associated with concentrations of actin and myosin under the capped membrane. Although these ligand-induced surface phenomena appear to be different on flat and rounded cells, we propose that in both cases clusters of receptors become linked across the membrane to actin- and myosin-containing structures. In flat cells these structures are very long stress fibers; therefore, when clusters of receptors become linked to these fibers, the clusters are immobilized. In round cells, membrane-associated actin- and myosin-containing structures are apparently much less extensive than in flat cells; therefore, clusters of receptors linked to these structures are still mobile in the plane of the membrane. We suggest that in this case the clusters are then actively collected into a cap by an analogue of the muscle sliding filament mechanism. To explain the transmembrane linkage, we propose that actin is associated with the plasma membrane as a peripheral protein which is directly or indirectly bound to an integral protein (or proteins) X of the membrane. Individual molecules of any receptor are not bound to X, but after they are specifically clustered into patches, a patch of receptors then becomes bound to S and hence to actin/myosin.

Actins↗
PubMed1984

Capping of the surface OKT3 binding molecule prevents the T-cell proliferative response to antigens: evidence that this molecule conveys the activation signal.

The human T-lymphocyte receptor for antigen appears to have been localized to a cluster of associated surface glycoprotein molecules, among which is the OKT3 binding molecule. We have tested the hypothesis that selective removal of the OKT3 binding molecule eliminates the cellular immune response to antigens by clearing the surface of the molecule that conveys the activation signal. Enriched T cells were obtained from donors immune to purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), or keyhole limpet hemocyanin (KLH). T-3 molecules were cleared from the cell surface by capping with OKT3 and F(ab')2 goat anti-mouse IgG. Regeneration of surface molecules was prevented by culturing the T-3 capped cells with OKT3 625 ng/ml. The capacity of capped T cells to proliferate in culture with antibody in response to antigens, alloantigens, and the mitogens, PHA and ionophore A23187, was compared to uncapped cells pretreated with media and to capped cells permitted to regenerate the OKT3 binding molecule. T-3 capped cells cultured in the presence of antibody failed to proliferate to antigens or alloantigens. However, T-3 capped cells cocultured with antibody also did not significantly proliferate to PHA, but did respond to A23187. In contrast, both media-treated T cells and cells which had regenerated the OKT3 binding molecule proliferated to mitogens, antigens, or alloantigens. The requirement for the OKT3 binding molecule was determined by utilizing T-1, T-4, and T-8 capped cells. T-1, T-4, or T-8 capped cells cultured in the presence of OKT1, OKT4, or OKT8 proliferated in response to antigens, alloantigens, and mitogens. These results demonstrate that in the absence of the OKT3 binding molecule, antigens, alloantigens, and PHA failed to induce a significant cellular proliferative response. In the absence of this molecule, PHA cannot bind to its carbohydrate moiety, and therefore cannot activate T cells to proliferate. These data support the concept that the molecule binding OKT3 conveys the transmembrane signal resulting in cellular activation.

Adult↗
PubMed1984

Concanavalin A receptors on the surface membrane of lymphocytes from patients with acute leukemia.

Peripheral blood mononuclear cells (PBM) isolated from 23 patients with acute lymphoblastic leukemia (ALL) and 24 with acute non-lymphoblastic leukemia (ANLL) were studied for binding and mobility of Concanavalin A (Con A) receptors, using fluorescent Con A (F-Con-A). The cap forming ability of PBM from all patients was 18.7 (+/- 9.3%) and 18.9 (+/- 9.9%) for ANLL patients at the time of diagnosis or during relapse. During clinical complete remission the cap forming ability of the PBM did not change significantly. No correlation was observed between the percentage of blasts present in the peripheral blood at the time of examination and the extent of cap formation, for both types of leukemia. The pattern of F-Con-A binding to PBM in ANLL patients was different compared to that seen in ALL. In ANLL, the fluorescent stain was concentrated in a round body on the cell ("button form") after binding to the membrane, while the rest of the cell showed almost no fluorescence. The present results indicate that PBM cells from patients with acute leukemia are characterized by a high degree of Con-A receptor mobility.

Cell Membrane↗
PubMedDate not supplied

Differential effects of propranolol on lymphocyte rosette formation and response to plant mitogens.

The effects of propranolol on various lymphocyte functions were studied to gain a better understanding of the recently demonstrated suppressive effect of propranolol on rheumatoid factor production. D- and L-propranolol at a concentration of 1 X 10(-4)M inhibited the formation of human EA rosettes. The inhibition occurred within one minute of adding the compounds, was reversible, and did not affect cell viability. Addtion of propranolol to preformed EA rosettes failed to disaggregate them. Patching and capping of SIg by an Fab'2 anti-IgG were inhibited at 2.5 X 10(-5)M and above. Propranolol at 2.5 X 10(-5)M also inhibited lymphocyte response to phytohemagglutinin and pokeweed mitogen without evidence of cell toxicity by trypan blue staining or absolute numbers of surviving cells. Congeners of propranolol with mainly beta adrenergic blocking properties did not show inhibitory effects. The inhibitory activities of propranolol are interpreted in terms of propranolol's membrane stablizing effects and ability to interfere with membrane receptor movement.

Animals↗
PubMed1980

Effects of linoleic acid on capping, lectin mediated mitogenesis, surface antigen expression, and fluorescent polarization in lymphocytes and BHK cells.

The incubation of linoleic acid with cells causes profound effects on membrane asociated phenomenon. Using the fluorescent probe diphenyl hexatriene (DPH) to monitor lipid changes in the microenvironment of the cell surface, we find that linoleic acid reduces the polarization values (P) in mouse lymphocytes and BHK cells. Measurements on lipids extracted from the cells grown in linoleic acid produce similar results. We also find in the mouse lymphocyte that capping of Ig is inhibited and con A stimulated mitogenesis is unaffected. In contrast to the latter effect, LPS and PHA stimulated mitogenesis is inhibited and in the rat lymph node, con A stimulated mitogenesis, greatly enhanced. We also show that linoleic acid alters the binding of antibodies to the cell surface of EL-4 lymphoma cells. These observations suggest that linoleic acid alters cellular function by interfering with protein/lipid interactions within the surface membrane.

Animals↗
PubMed1978

Systemic membrane defect in the proximal muscular dystrophies.

We studied lymphocyte capping in 61 patients with Duchenne, Becker, limb-girdle, facioscapulohumeral and congenital muscular dystrophies. All showed a markedly diminished percentage of capped cells when compared with 86 normal controls, providing support for previous evidence that an alteration in membrane fluidity may be a common pathogenic feature in several genetically distinct forms of proximal muscular dystrophy. Heterozygous carriers of Duchenne muscular dystrophy showed diminished capping that was indistinguishable from that of afflicted males and was often present even when serum enzyme levels were normal. Studies in 25 families with 16 suspected sporadic cases indicated that no more than four out of 30 afflicted males may represent new mutations. These findings imply that most cases of Duchenne dystrophy might be prevented by a population screening program for carrier females combined with prenatal detection of afflicted males.

Adolescent↗
PubMed1989

A cytotoxic monoclonal antibody that binds to human B cells, T cells, monocytes, and a subset of lymphomas.

Monoclonal antibodies have been derived against a variety of antigens on human leukocytes. We describe a complement-fixing, IgG2a, murine monoclonal antibody that was derived against ARH-77, a human plasma cell line. In a Western blot of a lysate of ARH-77, anti-ARH-77 recognized a 155 kD protein. On normal B cells, the antibody co-capped with surface immunoglobulin. Analysis of blood and lymph nodes indicated that the determinant recognized by the antibody is expressed by most B cells, T cells, monocytes, and lymphomas with surface immunoglobulin. The determinant was not present on granulocytes, platelets, mantle zone lymphocytes, or serum immunoglobulin. We conclude that anti-ARH-77 is a cytotoxic monoclonal antibody that recognizes a determinant shared by human mononuclear leukocytes. The determinant may be an exposed part of a membrane anchor or bridging protein associated with receptors on mononuclear cells.

Animals↗
PubMed1991

Mapping trajectories of Pgp-1 membrane protein patches on surfaces of motile fibroblasts reveals a distinct boundary separating capping on the lamella and forward transport on the retracting tail.

Patches of aggregated membrane proteins on motile fibroblasts are transported from the surfaces of the leading lamella to a site just ahead of the nucleus in the phenomenon known as capping. A major cell surface glycoprotein, Pgp-1 (GP80), was tagged with a monoclonal IgG and then aggregated with fluorescent secondary antibodies. Correlated digitized fluorescence and phase-contrast microscopy were used to map the trajectories of fluorescent Pgp-1 patches located in various regions of the cell surface. The response of patches located in lamellar and nonlamellar regions to spontaneous retraction of the trailing cell margin, or tail was examined in detail. During capping, Pgp-1 patches accumulated at a morphologically distinct site on the cell surface, the 'null border', corresponding to the boundary between lamelloplasm and endoplasm and the posterior edge of the dorsal cortical F-actin sheath. Posterior to this site, gradual forward movement of patches accompanied the gradual narrowing phase of the trailing edge retraction that occurs prior to abrupt detachment of the tail, but patches did not actually accumulate at the null border. The rate of forward patch movement was generally greater at positions further behind the boundary. Patch movement correlated approximately with forward organelle movement in the trailing region of the cell. The boundary was also apparent during simultaneous capping and retraction when forward patch transport on the trailing edge and rearward transport of patches across the lamellar surface appeared to converge on the null border. Forward patch transport was strictly confined to regions behind the boundary while retrograde patch transport was confined to the lamellar region ahead of the boundary. Patches are thought to be linked to the cortical cytoskeleton and their transport is discussed in terms of the very different cortical cytoskeletal dynamics occurring in the leading and trailing edges of locomoting cells.

Actins↗
PubMed1982

Molecular heterogeneity of D-end products detected by anti-H-2.28 sera. III. Reactivity of certain anti-H-2.28 alloantisera with Qa-2 antigen.

In capping experiments with peripheral T lymphocytes, two anti-H-2.28 sera (AKR anti-AKR.L, anti-Kb, and C3H anti-C3H.B10, k anti-b) that do not contain any Qa-2-specific antibodies are able to redistribute not only the H-2.28-positive H-2 molecules, but also Qa-2 molecules. This is due to the capacity of these sera to react with Qa-2 molecules because on cells where all known molecules of the H-2d haplotype were capped (K1d, K2d, Dd, Md, Ld, L2d), both antisera still reacted when the cells came from a Qa-2 positive Dd strain (B10.A) but not when the cells were of Qa-2 negative strain (BALB/cByA). The reaction with Ia and non-H-2 antigens was excluded in these experiments. These data show that Qa-2 and H-2 antigens share some specificities of the H-2.28 family. Other anti-private and anti-public anti-H-2 sera failed to react with the Qa-2 molecules.

Animals↗
PubMed1985

Morphine depression of T cell E-rosetting: definition of the process.

Two kinetic assays were developed to assess opiate effects on rates of T cell E-rosetting. The first adopted the thermal conditions of active E-rosetting assays (varying between 37 and 23 C) whereas the second incorporated cooler thermal conditions (varying between 0 and 29 C). In vitro treatment of lymphocytes with morphine depressed E-receptor levels and E-rosetting in both assays. With the 0-29 C procedure early stages of E-rosette formation were characterized by phase transition kinetics indicative of sequential gain and loss of E-rosettes. Assay thermal and erythrocyte (E) to T cell contact conditions, and the inclusion of morphine during E-rosetting, were independent variables that coordinately modulated the expression of phase transitions. Phase transitions were also noted during capping of total T cell E-rosettes at 37 C. The reason for phase transitions appears to be that T cells undergo sequential cycling of E-receptors, increasing because of the new expression of dormant E-receptors as the result of E-receptor microdisplacement and decreasing because E-rosettes are lost owing to patching and capping processes. According to this construction of the E-rosetting process, morphine inhibits E-rosetting and modulates expression of phase transitions by interfering with E-receptor microdisplacement processes. Presumably this interference by morphine is mediated through alteration of membrane fluidity and promotion of E-receptor coupling (and/or inhibition of uncoupling) to a transducer-effector component within the cell membrane. These findings and conclusions are specifically relevant to immunoregulatory processes and are also helpful for understanding the general nature of biological and physiological responses associated with receptor-ligand interactions.

Erythrocytes↗
PubMed1982

Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells.

Specific binding (conjugation) of cytotoxic T lymphocytes (CTL) to target cells (TC) is the first step in a multistage process ultimately resulting in dissolution of the TC and recycling of the CTL. We examined the position of the microtubule organizing center (MTOC) of immune CTL bound to specific TC. Immunofluorescence labeling of freshly prepared CTL-TC conjugates with tubulin antibodies indicated that the MTOC in essentially all conjugated CTL but not in the conjugated TC were oriented towards the intercellular contact site. This finding was corroborated by electron microscopy examination of CTL-TC conjugates fixed either immediately after conjugation or during the lytic process. Antibody-induced caps of membrane antigens of CTL such as H-2 and Thy 1, did not show a similar relationship to the MTOC. Incubation of CTL-TC conjugates, 10-15 min at room temperature, resulted in an apparent deterioration of the microtubular system of conjugated CTL. It is proposed that the CTL plasma membrane proximal to the MTOC is particularly active in forming stable intercellular contacts, resulting in CTL-TC conjugation, and that subsequent modulation of the microtubular system of the CTL may be related to the cytolytic response and to detachment of the effector cell.

Animals↗
PubMed1977

Genetic dissection of the control of normal differentiation in myeloid leukemic cells.

Normal myeloid precursors and MGI(+)D(+) myeloid leukemic cells can be induced to differentiate to mature cells by the normal protein inducer MGI. The sequence of differentiation is the induction of C3 and Fc rosettes, C3 and Fc immune phagocytosis (IP), synthesis and secretion of lysozyme, and formation of mature macrophages and granulocytes. Mutant clones of myeloid leukemic cells have been isolated with differences in the time of induction of C3 and Fc rosettes and C3 and Fc IP, in which lysozyme was induced without going through the stage of Fc or C3 IP, and with differences in inducibility by MGI to mature macrophages or granulocytes. Only one out of five MGI(-)D(-) clones gave rise to MGI(+)D(+) mutants. The ability to obtain mutants from this clone was associated with its special chromosome constitution, and these mutants showed a change in their ability for cap formation by concanavalin A. The steroid inducer dexamethasone can induce in MGI(+)D(+) clones differentiation to macrophages but not to granulocytes. Differentiation by steroid inducer in different clones occurred either with or without induction of Fc rosettes and Fc IP, and induction of C3 rosettes was not always associated with induction of C3 IP. The use of mutants that differ in their competence to be induced by MGI or steroid inducer has shown that there are separate controls for the induction of C3 and Fc rosettes, C3 and Fc IP, lysozyme, macrophages, and granulocytes.

Animals↗
PubMed2003

Clustering of the B cell receptor is not required for the apoptotic response.

We examined the role of BCR cell membrane redistribution in anti-IgM-induced apoptosis in three human B cell lines, RA#1, 2G6, and MC116, that differ in their relative levels of sIgM expression. The apoptotic response was found to be dependent on the nature of the anti-IgM and the cell line. In the cell lines, RA#1 and MC116, sIgM aggregated into patches that were insensitive to the disruption of cholesterol-rich membrane microdomains by nystatin or beta-MCD. The B cell line 2G6 was able to reorganize sIgM into a tight coalescent cap upon anti-IgM treatment. However, in this case, the lipid raft inhibitors nystatin and beta-MCD disrupted the patching. In 2G6 cells, BCR-mediated apoptosis was not affected by nystatin treatment, whereas it increased in beta-MCD pretreated cells. Thus, no evident correlation was found between apoptosis and BCR cell membrane redistribution or lipid raft formation in either of the three cell lines. The data indicate that the apoptotic signal transduction pathway is independent of BCR translocation into lipid rafts and/or aggregation.

Antibodies, Anti-Idiotypic↗
PubMed1997

Effects of Ajoene on lymphocyte and macrophage membrane-dependent functions.

Ajoene, (E, Z) -4, 5, 9-trithiadeca-1, 6, 11-triene 9 oxide, is a compound originally isolated from ethanolic extracts of garlic that impairs platelet aggregation by inhibiting the functional exposure of platelet integrins GPIIb/IIIa. In vitro, Ajoene is toxic for several tumoral cell lines, and exert an antiproliferative effect on T. cruzi and murine malaria parasites. Here we show that Ajoene strongly inhibited the proliferation induced in human lymphocytes by the mitogens phytohemagglutinin (PHA), phorbol myristate acetate (PMA) and anti-CD3, and the capping formation induced in B lymphocytes by anti-IgM antibodies. On macrophages, Ajoene was also found to partially inhibit the lypopolysaccharide-induced production of Tumor Necrosis Factor (TNF), and to decrease the phagocytic activity of thioglycolate-elicited mouse peritoneal macrophages for IgG-opsonized, human erythrocytes. Ajoene also partially prevented the lytic effect of human and rabbit TNF on Actinomycin D-treated WEHI 164 cells. These results strongly suggest that Ajoene is a potent modulator of membrane-dependent functions of immune cells.

Animals↗
PubMed1983

C-reactive protein antigenicity on the surface of human lymphocytes.

We reported previously that C-reactive protein (CRP), when complexed to a multivalent binding specificity, can bind to a subset of lymphocytes that bear the IgG Fc receptor. Recently we showed that anti-CRP plus complement depletes natural killer function. We now show the detection of CRP on the surface (S-CRP) of a small percentage of PBL and on a minor population of phagocytic mononuclear cells. S-CRP is not detectable by direct immunofluorescence, but is readily discernible by using more sensitive techniques such as biotinylated anti-CRP with fluorescent avidin or indirect immunofluorescence with monoclonal anti-CRP. S-CRP is expressed in the absence of calcium, whereas the binding of complexed CRP is calcium dependent. S-CRP does not appear to be the exclusive binding site for CRP-CPS because anti-CRP does not block the binding of complexed CRP. Both the binding site for complexed CRP and S-CRP can be capped off; however, the kinetics of capping of these two surface molecules is different. Cells binding complexed CRP are OKT11-, whereas a significant number of PBL bearing S-CRP are OKT11+. Therefore cells bearing S-CRP appear to be a separate population from those that bind complexed CRP. These studies establish the presence of S-CRP on a subpopulation of lymphocytes, define conditions required for its detection, and speak to certain of the relationships between S-CRP and the binding site of CRP-CPS complexes.

Antibodies, Monoclonal↗