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K Beiske

Publications and source records attributed to K Beiske.

50 records · Page 3Linked to original sources

Transforming growth factor type beta (TGF beta) inhibits G1 to S transition, but not activation of human B lymphocytes.

Type beta transforming growth factor (TGF beta) is a polypeptide that may influence the growth of a variety of cell types in a positive or negative fashion. In this study we show that TGF beta markedly inhibits DNA synthesis in normal and neoplastic human B lymphocytes stimulated to proliferate with anti-immunoglobulins and B-cell growth factor (BCGF). Although TGF beta was needed during the initial 12 h of the culture to promote optimal inhibition, we found that it had little or no effect on several early to intermediate parameters of cell activation [( Ca2+]i increase, c-myc mRNA increase, cellular enlargement, RNA increase, and the increase in the expression of the 4F2 activation antigen). In contrast, TGF beta almost completely blocked the induction of transferrin receptor expression, which normally occurs in the late G1 phase of the cell cycle. Therefore, we conclude that TGF beta treatment leads to arrest of the cells in the middle to late G1 phase, prior to transferrin receptor expression.

Antibodies, Anti-Idiotypic↗

Single cell studies on the immunological marker profile of plasmacytoid T-zone cells.

Plasmacytoid T cells (PTC) are known to home to thymic (T) zones in human lymph nodes and are characterized by their abundant, concentrically layered, rough endoplasmic reticulum. These cells have been found in reactive and neoplastic conditions. Three cases of PTC lymphomas have so far been reported. All of them were complicated by a myelomonocytic leukemia leading to the assumption of a functional relationship between PTC and the myeloid system. The immunologic phenotype of PTC, as revealed on frozen tumor tissue sections, comprised the expression of CD5 (T1), CD4 (T4), and HLA-DR, but not CD8 (T8) and CD2 (T11) and suggested an affiliation to the T cell system. Extending our previous report on one of these cases we here present the first study on the immunological marker profile of suspended PTC. The employment of unfractionated or PTC-enriched tumor cell suspensions rendered possible the application of a panel of monoclonal antibodies (moAbs) on both fixed and unfixed cells and enabled us to allocate various markers either to the intracytoplasmic or surface domain of this cell type. Our results suggest that PTC from our case rest in the G0/G1 phase of the cell cycle. They express the transferrin receptor, but not the Il-2 receptor (CD25) or the nuclear antigen Ki-67. No T cell antigen was demonstrated on the surface of unfixed suspended PTC. Under these conditions only HLA-DR and a predominantly monocytic antigen (CD36/moAb 5F1) were identified. Fixed cells, however, showed a weak cytoplasmic reactivity for CD5 and two myelomonocytic antigens (CD15/moAb 1G10 and CD14/moAb My4). Our findings do not sustain positive evidence for a T cell nature of PTC. Whether their phenotypical pattern indicates terminal differentiation with concomitant loss of T cell antigens or points to a cytogenetic relationship of PTC to the myeloid system, remains speculative. Until the cytogenesis of PTC is clarified we propose the noncommitted term "plasmacytoid T-zone cells" for this elusive cell type.

Antigens, Differentiation, T-Lymphocyte↗

T-zone lymphoma with predominance of 'plasmacytoid T-cells' associated with myelomonocytic leukaemia--a distinct clinicopathological entity.

In this paper we present a further case of a new clinicopathological entity combining a rare type of non-Hodgkin lymphoma with a myelomonocytic leukaemia. The characteristic feature of the lymphoma is massive infiltration of the T-zones of lymph nodes by plasmacytoid cells originally described by Lennert in non-specific lymphadenitis. Two lymphoma cases of this type have recently been published, by Müller-Hermelink et al. who named the cells 'plasmacytoid T-cells' (PTC), and by Prasthofer et al. These three cases have similar clinical and pathological features and appear to form a distinct clinicopathological entity. In contrast to the two previously published cases the present lymphoma also contained irregular lymphoid cells accompanying the PTC in the lymph node lesion and focally infiltrating the bone marrow. An accumulation of polytypic IgG positive plasma cells was observed in the remaining lymph node follicles. Immunohistological analysis with a range of monoclonal antibodies showed the PTC of our case to be CD5(T1)+, CD4(T4)+, CD3(T3)-, CD8(T8)-, CD2(T11)-, and CD25(TAC)-, but HLA-DR+ and transferrin receptor positive. The nature of this peculiar lymphoid lesion and its relationship to myelomonocytic leukaemia are discussed.

Aged↗

Characterization of human mononuclear cells after positive selection with immunomagnetic particles.

We have investigated the possibility to employing magnetic monodisperse polymer particles for positive selection of human peripheral blood mononuclear cell populations. By carefully titrating the ratio between particles and cells we succeeded in isolating a number of cell populations that could be cultivated subsequently in vitro for functional studies. The success of the procedure is partly dependent on the properties of the monoclonal antibodies used to sensitize the cells. Provided these antibodies do not react with membrane structures involved in the transduction of activating signals, highly purified, quiescent cell populations can be recovered in a single fractionation step. In most instances particles will detach from the isolated cells by overnight culture, and the particles can then be removed from the system by a suitable magnet. T lymphocytes, subpopulations of T lymphocytes, and B lymphocytes have been isolated in this way and studied in a variety of functional assay systems. Comparison with cells obtained after negative selection clearly demonstrates the usefulness of this technique, especially if the membrane marker selected for it is not directly engaged in the activation processes.

Antibodies, Anti-Idiotypic↗

The specific induction of myc protooncogene expression in normal human B cells is not a sufficient event for acquisition of competence to proliferate.

Resting human B cells can be activated to proliferate in the presence of both polyclonal antibodies to immunoglobulin mu heavy chains and B-cell growth factor (BCGF). This process appears to be temporally controlled in that the initial activation of the B cells and their responsiveness to BCGF is carried out by polyclonal anti-mu-chain antibodies alone. We have used this system to investigate the role of the c-myc gene in the cell cycle of normal human peripheral blood B cells. Our results show that the polyclonal anti-mu-chain antibody-induced B-cell activation is accompanied by a specific induction of c-myc gene expression without promoting subsequent entry into the S phase unless BCGF is added. Monoclonal antibodies to either mu chain or the pan-B-cell antigen Bp35 also revealed a similar G0-to-G1 transition and activation of c-myc gene expression. However, unlike activation with polyclonal anti-mu-chain antibodies, cells stimulated with these monoclonal antibodies do not acquire responsiveness to BCGF. The results imply that additional inducible functions must be present to potentiate the myc-specific function in order for the B cells to acquire the capacity to proliferate in response to BCGF. These findings are discussed in relation to the origin of B-cell malignancies.

Antibodies, Anti-Idiotypic↗

Different fate of antibodies to surface IgM and IgD in germinal centre cell-associated lymphomas.

In all of four human germinal centre cell-associated B lymphomas carrying sIgM + sIgD F(ab')2 fragments of rabbit antibodies to human mu-chain were accumulated intracellularly, whereas the accumulation of antibodies to delta-chain was considerably less abundant. The accumulation of antibodies to light chain was intermediate between antibodies to mu- and delta-chain. These results could be explained by the following observations: (i) the difference in the level of reexpression of sIgM and sIgD and (ii) the discovery that antibodies to delta-chain bound to reexpressed sIgD were degraded at a higher rate than those bound to primary sIgD and at a higher rate than antibodies to mu-chain, whether bound to primary or reexpressed sIgM.

Absorption↗

Induction of maturation in different types of B-cell lymphomas in vitro with TPA and antibodies to surface immunoglobulin.

Cells from eight selected cases of human non-Hodgkin lymphomas of various histological types (lymphocytic, centrocytic, centrocytic/centroblastic, and immunocytomas) were stimulated in vitro with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and anti-immunoglobulins (anti-Ig) against the surface immunoglobulin (sIg) on the tumour cells. Six of these cases responded by intracellular Ig accumulation as measured by flow cytofluorometry and direct phenotypical change into immunoblasts/plasmablasts as detected by light microscopic immunocytochemistry. However, the response to TPA alone varied considerably from case to case. These findings suggest that many, if not all, B-cell subsets have the capacity to develop directly into Ig-synthesizing cells (immunoblasts and plasmablasts). However, conditions for eliciting such events may vary, depending on the phenotypical properties and differentiation stage.

Antibodies, Anti-Idiotypic↗

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↗

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↗