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B Dugas

Publications and source records attributed to B Dugas.

106 records · Page 6Linked to original sources
PubMed1986

Human B cell activation: selective sensitivity of the early stages to calcium channel-blocking drugs.

The importance of Ca2+ in the early events of lymphocyte activation has been suggested by several studies. We examined the effect of calcium channel-blocking drugs (verapamil and nitrendipine) on the progression of human B cells through their activation cycle. Our results show that these drugs suppress the anti-mu-induced human B cell proliferation and interfere with the early events of the B cell activation in a dose-dependent fashion. This suppression correlates with a marked decrease in anti-mu-induced 45Ca2+ uptake. Calcium channel-blocking drugs inhibit the anti-mu-induced uridine incorporation and the appearance of the activation marker defined by the 4F2 monoclonal antibody. Calcium channel-blocking drugs also inhibit B cell proliferation induced by the costimulation with anti-mu antibody and B cell growth factor (BCGF). However, this inhibition takes place at the early (anti-mu-dependent) stage of B cell activation: the BCGF-dependent proliferation of in vitro anti-mu-activated B cells is only marginally inhibited. Finally the proliferation of Epstein-Barr virus-infected B cell lines is resistant to the effect of calcium channel-blocking drugs.

Antigens↗
PubMed1986

Differentiation factors for human specific B cell response.

Nonspecific T cell factors produced by lectin-activated human peripheral blood lymphocytes (PBL) were used to restore the T-dependent B cell response to trinitrophenyl-polyacrylamide (TNP-PAA). Preincubation experiments with the particulate antigen TNP-PAA and/or a soluble TNP-protein conjugate show that a first specific signal provided by the antigen and nonspecific lymphokines sequentially acts on B cells. By gel filtration the T cell-replacing factor (TRF) activity is present in the 30-15-kDa fraction of T cell supernatants and is associated to interleukin 2 (IL2). However, absorption of IL2 does not abolish the TRF activity. Moreover, chromatofocusing of this 30-15-kDa material allows the obtaining of an IL2-free fraction containing a differentiation factor (with an isoelectric point of 5.7 +/- 0.2). The ability of this fraction to restore the anti-TNP response is manifest in the presence of a 50-kDa B cell growth factor. This latter, prepared by a combination of absorption on concanavalin A-Sepharose and gel filtration, was IL2 free and unable to support the anti-TNP response. We thus directly demonstrate that in the absence of IL2 three separate signals (the antigen, T cell-derived growth and differentiation factors) are involved in human-specific B cell response.

B-Lymphocytes↗
PubMed1986

B cell hyperactivity in systemic lupus erythematosus: selectively enhanced responsiveness to a high molecular weight B cell growth factor.

To characterize B cell hyperactivity in systemic lupus erythematosus (SLE) patients we studied the early events of B cell activation in 14 patients and controls. We measured B cell proliferation induced by three interleukin (IL) preparations (20-kDa B cell growth factor, BCGF, recombinant IL2 and 50-kDa BCGF) in the absence and in the presence of an anti-mu antibody (Ab). SLE B cells exhibited a markedly enhanced proliferative response to the 50-kDa BCGF in the absence of an anti-mu Ab, while responding normally in the presence of a first signal. This pattern of hyperactivity was observed in 11 out of 14 patients tested, and was absent in control patients. In contrast, SLE B cells behaved like normal B cells for the response to the other two IL tested, and to the anti-mu Ab alone. It should be pointed out that SLE B cells responded normally to recombinant IL2 whereas T cells from the same patients exhibited a decreased response to this IL. The selectively enhanced responsiveness of SLE B cells to the 50-kDa BCGF suggests that the events leading to B cell hyperactivity in this disease affect the early stages of B cell activation.

Adult↗
PubMed1986

Different human B cell subsets respond to interleukin 2 and to a high molecular weight B cell growth factor (BCGF).

After activation by anti-mu antibody human B cells acquire the ability to proliferate in the presence of recombinant interleukin 2 (IL 2), a 20-kDa mol. mass B cell growth factor (BCGF) and a high mol. mass BCGF (50-kDa BCGF). An anti-IL 2 receptor (IL 2R) monoclonal antibody inhibits the IL 2-dependent proliferation without affecting that induced by BCGF. B cells expressing the IL 2R after anti-mu antibody activation (IL 2R+ cells) were separated from those not expressing IL 2R (IL 2R- cells). IL 2 stimulated the proliferation of only IL 2R+ cells whereas the 20-kDa BCGF acted on both IL 2R+ and IL 2R- cells. Importantly, the 50-kDa BCGF supported the proliferation of IL 2R- cells whereas it was inactive on IL 2R+ cells. Thus, the B cell subset responding to the 50-kDa BCGF after anti-mu antibody activation is distinct from that responding to IL 2.

Antibodies, Monoclonal↗
PubMed1986

Early events in human B cell activation: metabolic pathways vary according to the first signal used.

The effects of the calcium channel blocking drug Verapamil and of palmitoyl-carnitine (PTC), an inhibitor of protein-kinase C activity, on human B cell activation were measured. Both Verapamil and PTC inhibited the B cell proliferation induced by costimulation with anti-mu antibody and with 3 different growth factors: interleukin 2, 20-kDa B cell growth factor and 50-kDa B cell growth factor. Both uridine and thymidine incorporation induced by costimulation with ionomycin and phorbol 12-myristate 13-acetate (PMA) were inhibited by Verapamil and PTC. In contrast, B cell proliferation was resistant to Verapamil (while being still inhibited by PTC) in two situations: when B cells were costimulated with PMA and growth factors and when B cells previously activated in vitro (by anti-mu antibody or PMA) were stimulated with growth factors. These results confirm that the late stage (G1----S transition) of B cell activation is independent of Ca2+ entry. More importantly, they show that the initial events induced by anti-mu antibody and by PMA are based on different biochemical pathways: PMA would act on a subpopulation of B cells which has already received an early signal of activation in vivo. This emphasizes the functional and biochemical heterogeneity of the G0 stage among circulating B cells.

B-Lymphocytes↗
PubMed1986

Presence of preactivated T cells in hemodialyzed patients: their possible role in altered immunity.

Interleukin 2 (IL-2) and B-cell growth factors I and II (BCGF I and BCGF II) are lymphokines produced by T cells that play a major role in T- and B-cell cooperation. Peripheral blood lymphocytes from 12 uremic patients undergoing intermittent hemodialysis were tested for their capacity to produce IL-2 and BCGFs and to respond to these soluble mediators. IL-2 and BCGF activities were determined by means of two biological assays (proliferation of IL-2-dependent cytotoxic T-cell line CTLL-2 and of anti-human IgM (mu chain)-stimulated normal B cells, respectively) in the supernatants of phytohemagglutinin A-stimulated T-cell cultures. IL-2 activity was significantly decreased in patients as compared to normal controls (mean +/- SEM, 0.28 +/- 0.09 unit per ml) in hemodialyzed patients versus 1.02 +/- 0.16 units per ml in normal controls). This profound abnormality contrasted with the normal activity of the BCGFs that was invariably observed in the same supernatants. A similar dissociation was detected when analyzing the sensitivity of uremic B and T cells to exogenous purified lymphokines. Anti-IgM (mu chain)-stimulated uremic B cells exhibited a normal response to recombinant IL-2 and to chromatography-purified BCGF I and BCGF II. Resting B cells did not show any increased reactivity to these lymphokines. In contrast, whereas in normal controls recombinant IL-2 exclusively induced the proliferation of T cells that had been previously activated by a mitogen, resting T cells from uremic patients were highly responsive to exogenous IL-2. This abnormal response was paralleled by significantly increased proportions of peripheral T cells recognized by the anti-Tac monoclonal antibody that specifically binds to the IL-2 receptor. These data clearly show the existence in hemodialyzed patients of abnormally high proportions of T cells presenting phenotypic and functional signs of preactivation. This increased T-cell IL-2 receptor expression may offer an explanation to the deficient IL-2 activity observed in patients' supernatants (by inducing increased absorption of the lymphokine). The potential relevance of these preactivated T cells to the depressed cell-mediated immunity observed in hemodialyzed patients is outlined.

Adult↗
PubMed1985

Functional properties of two human B cell growth factor species separated by lectin affinity column.

The supernatants from PHA-activated normal human T cells (conditioned medium) were fractionated by differential adsorption on Con A-Sepharose columns. The effluent contained both IL 2 activity (tested on the CTL-L2 cell line) and BCGF activity (tested on anti-mu-activated normal B-enriched cells). Absorption of such effluent on PHA-activated T cell blasts removed the IL 2 activity without affecting the BCGF activity. The eluate also displayed BCGF activity (tested on anti-mu-activated B-enriched cells) without detectable IL 2 activity. The two BCGF species isolated by this criteria synergize with semipurified IL 1 to support the anti-mu-induced proliferation of highly monocyte-depleted B cells. Both BCGF species required the presence of anti-mu Ab to support the proliferation of small B cells (at the G0 stage). However, in contrast to crude conditioned medium and to the BCGF present in the effluent, the BCGF present in the eluate was unable to induce the proliferation of unfractionated or large (at the G1 stage) B cells in the absence of anti-mu Ab. These results support the existence of two functionally different human BCGF species, differing at least in their relative sugar content and distinct from IL 2.

Adsorption↗
PubMedDate not supplied

The low affinity receptor for IgE (CD23) in human: a multifunctional receptor/cytokine?

This review relates the molecular and the functional aspects of the low affinity IgE receptor for IgE (CD23), and the possible cooperation with additional cytokines, lipid mediators and/or pharmacological agents (i.e. beta 2-adrenoceptor agonists etc ...) that appear to be involved in the regulation of the IgE-dependent immune and inflammatory responses in human. The possible contribution of CD23 to the initiation and the development of various diseases is also discussed.

Antigens, Differentiation, B-Lymphocyte↗
PubMedDate not supplied

Influence of interleukin-4 and platelet-activating factor on the Fc epsilon RII/CD23 expression on human monocytes.

Human recombinant interleukin-4 (IL-4) induces the expression of the low-affinity receptor for IgE (Fc epsilon RII/CD23) on human normal monocytes as assessed by flow cytometry. Also, platelet-activating factor (PAF) induces a time- and dose-dependent increase in Fc epsilon RII/CD23 expression, which is maximal with 1 microM PAF and after a 24-h incubation period. Under similar experimental conditions, lyso-PAF (1 microM) has no effect on Fc epsilon RII/CD23 expression. The PAF-induced Fc epsilon RII/CD23 expression on human monocytes is inhibited by two unrelated antagonists of the mediator, namely BN 52021 and BN 50730, but is not significantly affected when the cells are incubated in the presence of a rabbit anti-IL-4 antiserum. The IL-4-induced Fc epsilon RII/CD23 is abolished in the presence of the anti-IL-4 antiserum and slightly (not significantly) reduced when BN 52021 or BN 50730 is added to the incubation medium. These results suggest that PAF regulates Fc epsilon RII/CD23 expression and may indicate a new role for this autacoid in allergic diseases.

Antigens, Differentiation, B-Lymphocyte↗