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T Godal

Publications and source records attributed to T Godal.

At least 91 records · Page 5Linked to original sources

Induction of maturation of human B-cell lymphomas in vitro. Morphologic changes in relation to immunoglobulin and DNA synthesis.

In vitro stimulation of cells from 8 non-Hodgkin's lymphomas comprising several histologic types with a tumor promotor (TPA) and with or without anti-immunoglobulins directed against the surface immunoglobulin of the tumor cells is reported. Morphologic transformation to immunoblastic and plasmablastic cells, but not to plasma cells, and induction of Ig and DNA synthesis were observed. A comparative analysis, including flow cytofluorometry, light microscopy combined with immunocytochemistry, and electron microscopy, suggests that the three events may not always be associated phenomena at the single-cell level even in monoclonal cell populations.

B-Lymphocytes↗

Surface IgG subclasses in human B cell lymphomas as revealed by monoclonal antibodies.

IgG subclass expression on cells from lymph node biopsies of 17 sIgG positive B cell lymphomas has been studied. Subclass specific monoclonal antibodies were used in an immunoradiometric assay. Ten were also tested by immunofluorescence using a biotin-avidin system. Thirteen of the lymphomas expressed IgG only, while four co-expressed other Ig isotypes. Morphological investigations revealed that 14 lymphomas originated from germinal centre cells. IgG1 was found to be dominant subclass in 10 lymphomas, IgG3 in seven, IgG2 in one, while none expressed IgG4. Multiple IgG subclasses could not be detected in any of the lymphomas tested.

Antibodies, Monoclonal↗

T-cell conditioned media reverse T-cell unresponsiveness in lepromatous leprosy.

In some subjects the infective agent of leprosy, Mycobacterium leprae, causes disseminated (lepromatous) disease. Such subjects have a major role in the transmission of the disease and show deficient T-cell responses both in vivo and in vitro to M. leprae, but not to other antigens. Numerous studies have recently shown that T cells with functional capabilities after initial triggering with antigen can be maintained in a state of continuous proliferation in vitro when cultured in medium containing interleukin 2 (IL-2). Here we have studied the effect of IL-2 rich T-cell conditioned medium on lepromatous peripheral blood mononuclear cells. Our results show that although lepromatous T cells fail to produce IL-2 after exposure to M. leprae they can respond by proliferation to M. leprae in the presence of T-cell conditioned medium, suggesting that the unresponsiveness in lepromatous leprosy results from a deficiency in the production of IL-2 or related factors and not a lack of M. leprae-reactive T cells.

Culture Media↗

Expression of the BLA antigen, defined by the monoclonal 38.13 antibody, on Burkitt lymphoma lines, lymphoblastoid cell lines, their hybrids and other B-cell lymphomas and leukemias.

The BLA expression of eight Burkitt lymphoma lines was high, whereas it was negative in four, including the two IgG producers tested. Most lymphoblastoid cell lines (LCL) of normal origin had only a low percentage of positive cells, not significantly above background, although a few had up to 30% positives. EBV conversion of the EBV-negative Burkitt lymphoma line Ramos destabilized the high BLA expression, leading to a decrease in the average number of positive cells in the majority of the converted sublines in parallel with considerable fluctuation in antigen expression within each subline. Our group has previously shown that EBV-conversion of Ramos cells can induce certain differentiation steps (Spira et al., 1981 a). EBV-converted sublines of another EBV-negative Burkitt lymphoma, BJAB, showed a much greater stability previously and remained unchanged with regard to BLA expression in our present experiments. Eight T-cell leukemias, three myeloid leukemia lines and two diffuse histiocytic lymphomas were negative for BLA, whereas two myeloma lines were 30-40% positive. A histiocytic tumor had marginal reactions. Hybrids derived from the fusion of high with low BLA-reactive parental lines showed all three possible patterns (high, intermediate and low), provided that B-cell lines were fused with each other. Fusion of two Burkitt lymphoma lines with the K562 erythroleukemia line led to the extinction of BLA expression, as well as to the eclipse of other B-cell markers. B-lymphoma and leukemia (CLL) cells harvested directly from the patient showed a heterogeneous reactivity pattern. Strong to intermediate BLA expression was found among CLL cells and in most histological groups of B-CLL lymphomas except the centroblastic group (3/3 negatives). IgG-expressing follicular lymphomas were less reactive than IgM +/- IgD lymphomas of the same group. Immunocytomas were also low-reactive. BLA can be thus expressed on a variety of B-cell neoplasms; the degree of its expression appears to be related to the stage of differentiation.

Antibodies, Monoclonal↗

Early, anti-immunoglobulin induced events prior to Na+-K+ pump activation: an analysis in a monoclonal human B-lymphoma cell population.

Events following F(ab)2 anti-delta immunoglobulin stimulation of monoclonal (leukemic) human B cells prior to Na+-K+ pump activation were investigated in vitro. This pump activation, measured by ouabain-sensitive 86Rb+ uptake, appeared susceptible to the phospholipid-interacting drugs tetracaine and quinacrine, to the antioxydant nordihydroguaiaretic acid (NDGA), and to the calmodulin antagonist trifluoperazine, while much less susceptible to the methylation inhibitor-3-deazaadenosine. The Ca++ ionophore A 23187 appeared to induce pump activation in a way similar to anti-delta, as it was susceptible to the same drugs and as anti-delta had no additional stimulating effect on A 23187-stimulated cells. However, whereas the anti-delta-induced activations appeared independent of the extracellular Ca++ activity, [Ca++]e, the activation by A 23187 was potentiated by addition of the Ca++ chelator ethyleneglycol-bis (beta-aminoethyl ether) N, N'-tetracetic acid (EGTA). Estimations by fluorescent chelator method (quin 2) showed anti-delta to increase the intracellular Ca++ activity, [Ca++]i both in the absence and presence of EGTA. A 23187 increased [Ca++]i strongly in Ca++ medium, but was weaker, more similar to the anti-delta response, in EGTA medium. It is suggested that Na+-K+ pump activation after anti-Ig stimulation in B cells may follow Ca++ mobilization from internal stores. The trifluoperazine susceptibility suggests that calmodulin regulation is involved.

Antibody Formation↗

Sézary cells with an unusual phenotype, their modulation with 12-O-tetradecanoyl phorbol-13-acetate (TPA) in vitro, and their relationship to T-cell development.

Leukemic cells from a patient with Sézary syndrome were studied with a panel of monoclonal antibodies. Despite their typical morphology, the cells expressed an unusual surface phenotype. They simultaneously expressed OKT4 and OKT8 reactivity, indicating a more immature origin of the neoplastic cells than what has previously been observed in Sézary syndrome, but they were OKT6 negative. In response to 12-O-tetradecanoyl phorbol-13-acetate (TPA) the cells underwent phenotypic alterations, as the OKT4 reactivity was significantly reduced and the OKT8 expression was retained. Thus, following TPA, the cells expressed a surface phenotype consistent with the cytotoxic/suppressor T-cell subset in normal peripheral blood. The findings are discussed in relation to normal T-cell maturation and differentiation processes.

Aged↗

Amiloride inhibits anti-Ig induction of proliferation in a human B-lymphoma cell population.

The effects of amiloride on increased 86Rb+ influx, an early event of lymphocyte activation, and on the late event, [3H]thymidine uptake, were compared in anti-Ig-stimulated human B-lymphoma cells in vitro. Both events were inhibited to significant and comparable extents, and the drug effects were apparently not due to unspecific toxicity. This suggests that the increased 86Rb+ influx reflects early changes (e.g. amiloride-sensitive Na+-H+ exchange) which are required for anti-Ig induction of B-lymphocyte proliferation.

Amiloride↗

Different responses elicited in vitro by antibodies to IgM and IgD in cells from a surface IgM + D-positive human follicular lymphoma.

The effect of anti-Igs in combination with the tumour promotor TPA on DNA and Ig synthesis in a human follicular germinal centre cell lymphoma carrying sIgM and sIgD was investigated. The lymphoma cells responded to both anti-mu and anti-delta chains and to anti-lambda light chains by DNA synthesis, as measured by methyl-(3H)-thymidine incorporation. Flow cytofluorometric measurements, however, showed that only anti-mu chains induced marked increase in cytoplasmic Ig content. This result suggests that in certain B-cell subsets the signals elicited via sIgM and sIgD are different.

Antibodies, Anti-Idiotypic↗

Delineation of subsets in human B-cell lymphomas by a set of monoclonal antibodies raised against B lymphoma cells.

Murine hybridoma antibodies to a human B-cell lymphoma were developed. After screening against normal T cells, monocytes, and granulocytes 11 antibodies that reacted with cells from other B-cell lymphomas remained, of which 10 showed individually distinct staining patterns, as tested by indirect fluorescence. When tested against lymphomas or cell lines, none of these antibodies revealed staining patterns suggesting reactivity with conventional B-cell surface markers, such as immunoglobulin, complement factor 3 receptors, or HLA-DR antigens. Only one of the antibodies (GB1) reacted with human serum, as determined by a blocking assay. The antibodies were found to belong to different immunoglobulin isotypes. Two antibodies (GB13 and GB14) reacted with greater than 5% of normal peripheral blood mononuclear cells. These reactions were mainly due to reactivity with B cells. The antibodies reacted only in a few cases with acute leukaemias, B-cell lines, and follicular lymphomas. On the other hand, distinct patterns of reactivity in different histological groups of diffuse lymphomas were obtained, suggesting that the antibodies may be useful in delineating phenotypic subsets among human B-cell lymphomas.

Animals↗

In vitro induction of human suppressor T cells by mycobacterial antigens. BCG activated OKT4+ cells mediate suppression of antigen induced T cell proliferation.

Peripheral blood mononuclear cells (PBMC), obtained from BCG vaccinated healthy donors, were induced to proliferation by BCG for five days in vitro. When re-exposed to BCG, they failed to proliferate. However, they partially retained the ability to respond to Con A and allogeneic cells. The addition of graded numbers of such cultured cells to fresh autologous PBMC suppressed their proliferative response to BCG. These suppressor cells could also inhibit the proliferation of fresh cells to other mycobacterial antigens, both in particulate form, i.e. Mycobacterium leprae, or in soluble form, i.e. PPD and SPA30. However, these pre-cultured cells did not inhibit the response of fresh cells to non-specific mitogens, i.e. Con A and alloantigens. The inhibition of the response to non-mycobacterial soluble antigens, i.e. tetanus toxoid (TT) and diphtheria toxoid (DT) varied with little suppression in some individuals and stronger suppression in others. The suppression to BCG was found to be mediated by T cells. Subfractionation of T cells by monoclonal antibodies OKT4 and OKT8 allocated the suppressor cells to the OKT4+ class of T cells. The suppression in the autologous system was quite strong, whereas it was much weaker in allogeneic systems.

Antibodies, Monoclonal↗

Natural killer cell activity is closely associated with a growth-inhibitory serum protein with protease-like activity.

A correlation between natural killer (NK) cell activity and growth inhibition (GI), as measured in an in vitro assay with B16 melanoma cells, mediated by a serum growth-inhibitory factor (GIF), among various strains of mice has been demonstrated. Beige mice (bg/bg), known to express low NK-activity, were also low in GIF activity and showed increased susceptibility to both B16 melanoma cells and another solid tumor (Lewis lung carcinoma) in vivo. In vivo treatment with various protease inhibitors that reduced NK-activity, also reduced growth inhibition mediated by GIF. Protease inhibitors that did not affect NK-activity did not affect GIF either. All of 4 B16 melanoma clones selected against GIF in vitro and resistant to GIF showed both resistance to NK-cells in vitro and increased growth potential in vivo. However, P-815, an NK-resistant cell line, was sensitive to GIF.

Animals↗

Triggering of monoclonal human lymphoma B cells with antibodies to IgM heavy chains: differences of response obtained with monoclonal as compared to polyclonal antibodies.

A comparative study of human B lymphoma cells activation by monoclonal (murine hybridoma) antibodies to mu heavy chains (Ma-mu) as compared to polyclonal (rabbit) antibodies to mu heavy chains (Ra-mu) has been carried out. Early events related to calmodulin activation such as 86Rb influx and changes in cell volume at 4 h could be induced by Ma-mu. One antibody (AF6) approached Ra-mu with regard to the strength of response obtained. However, Ma-mus including AF6 were deficient in inducing DNA synthesis under conditions where this was achieved with Ra-mu. Studies in one lymphoma, where stimulation of re-expressed surface IgM could be studied, revealed that Ma-mu was deficient in stimulating re-expressed sIgM. These findings raise questions with regard to polyclonal antibody to surface Ig as a model for B cell triggering by antigen and suggest that antigen-induced B cell triggering may be more complex than indicated by previous studies with polyclonal antibody.

Antibodies, Monoclonal↗

Monoclonal human B lymphoma cells respond to DNA synthesis to anti-immunoglobulins in the presence of the tumour promotor TPA.

Monoclonal human B lymphoma cells were triggered in vitro to DNA synthesis with F(ab')2 fragments of rabbit IgG antibodies specific for different human immunoglobulin (Ig) light and heavy chains. The specificity of the responses corresponded to surface Ig (sIg) present on tumour cells. Anti-mu chain, anti-delta chain, and antibodies to light chains were found to mediate this effect. However, to induce DNA synthesis, the tumour promotor 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was usually required. TPA alone induced cytoplasmic protrusions and increases in cellular volume. These observations should provide new opportunities to study the triggering of B cells with anti-Ig in well-defined cell populations.

Antibodies, Anti-Idiotypic↗