Biomedical subjects

B Dugas

Publications and source records attributed to B Dugas.

At least 55 records · Page 3Linked to original sources

PubMed1994

Beta 2-adrenoceptor agonists regulate the IL-4-induced phenotypical changes and IgE-dependent functions in normal human monocytes.

The beta 2-adrenoceptor agonists salbutamol and fenoterol were tested for their regulatory effects on human monocyte phenotype and functions, either alone or in combination with interleukin-4 (IL-4). These drugs enhanced in a dose-dependent manner the IL-4-induced membrane and mRNA expression of the low-affinity receptor for immunoglobulin E (IgE) (CD23), as well as the release of its soluble form, sCD23. Salbutamol and fenoterol alone elicited expression of the monomorphic beta 2-chain (CD18) of the leukocyte functional antigen (LFA1) family. This effect appeared to be restricted to CD11b (CR3) and CD11c (gp 150-95), because CD11a (LFA-1 alpha chain) was not modified. beta 2-Adrenoceptor stimulation was also found to potentiate the effect of IL-4 on CD11b, CD11c, and CD18 expression. In contrast, these agents alone did not alter the level of major histocompatibility complex class II and CD14 antigens or modify their respective up- and down-regulation by IL-4. Ligation of CD23 on IL-4-preincubated (CD23+) monocytes with IgE/anti-IgE immune complexes induced the release of free radicals nitric oxide and of the proinflammatory mediators IL-6 and thromboxane B2 (TxB2). Addition of salbutamol, inactive alone, potentiated the generation of superoxide anion and of nitric oxide generation, as well as the production of IL-6 and TxB2 triggered by CD23 ligation. These results indicate that beta 2-adrenoceptor stimulation potentiates in vitro the IL-4-induced phenotypical and functional changes on monocytes and suggest that such an interaction could occur in IgE-dependent immune reactions.

Albuterol↗

PubMed1994

Heterogeneous spontaneous and interleukin-4-induced nitric oxide production by human monocytes.

The generation of nitric oxide by human monocytes has long been a subject of controversy because of the difficulty of rationalizing this production. In this work we evaluated the capacity of human monocytes to produce nitric oxide (NO) as measured by nitrite (NO2-) release. Resting unstimulated monocytes (2 x 10(6) cells/ml) were found to produce significant amounts of NO2- after 8 to 12 days in culture. This production appeared to be highly heterogeneous. Indeed, approximately, 75% of monocytes from the different donors produced up to 10 microM NO2- and were considered low producers; the last 25% produced higher amounts of NO2- (from 10 to 110 microM) and were considered high producers. In any case the spontaneous production of NO2- by monocytes was overcome in the presence of 1 mM N omega-monomethyl-L-arginine (LNMMA). This inhibitory effect was reversed in the presence of an excess of L-arginine (5 mM), indicating that this process is effectively dependent on L-arginine metabolism. Because interleukin-4 (IL-4) is considered an important NO-regulatory cytokine, its regulatory effect on this spontaneous production of NO was also evaluated. In the presence of a defined dose of IL-4 (1 to 100 ng/ml) the spontaneous production of the high-producing population of monocytes was abrogated, whereas IL-4 stimulated the production by the low-producing population of monocytes, which was suppressed in the presence of LNMMA. The present data indicate that NO production by human monocytes is heterogeneous and that IL-4 can be a potent inducer or inhibitor of this production, suggesting a variability in the activation state of these cells.

Arginine↗

PubMed1994

Leukotriene B4 enhances IL-4-induced IgE production from normal human lymphocytes.

Interleukin 4 (IL-4)-induced IgE production by normal peripheral blood mononuclear cells (PBMC) and E- cells (PBMC partially depleted of T cells) was significantly enhanced by leukotriene B4(LTB4) in a dose-dependent manner, whereas LTB4 by itself was not effective for IgE production. The potentiating effect of LTB4 was strictly dependent on IL-4. When PBMC or E- cells were primed with IL-4 (300 U/ml) for 48 hr, then recultured with LTB4 alone (10(-10) to 10(-8) M), increased IgE production was observed. Maximum enhancement of IgE production after IL-4 priming was achieved using a combination of IL-4 and LTB4, acting additively. Moreover, the potentiating effect of LTB4 on IL-4-induced IgE production was completely dependent on the presence of a monocyte/macrophage population. This effect of LTB4 was completely abolished by depletion of monocytes and recovered by reconstitution with autologous monocytes. From the study of IL-4 receptor (IL-4R) expression determined by flow cytometry, IL-4 was found to upregulate the biotinylated-IL-4 (B-IL-4)/streptavidin binding to both T- and B-cell populations. A further increase of B-IL-4 binding was obtained when the cells were incubated with IL-4 and LTB4. Finally, LTB4 can induce soluble CD23 (sCD23) release by E- cells tested either alone or in the presence of IL-4. Taken together, these data suggest that LTB4 can influence the IL-4-induced IgE production through, at least, a bimodal action, i.e., increase of IL-4R positive cells and release of sCD23. These findings may be a specific feature of LTB4 which provides a crucial role in IL-4-linked allergic inflammatory process.

Humans↗

PubMed1994

Mononuclear cells from infants allergic to cow's milk secrete tumor necrosis factor alpha, altering intestinal function.

BACKGROUND/AIMS: Intestinal dysfunction observed during cow's milk allergy (CMA) is incompletely understood, and neither the effector cells nor the mediators responsible have been clearly identified. This study was undertaken to better characterize the implication of mononuclear cells in food allergy. METHODS: Peripheral blood mononuclear cells (PBMC) from infants with CMA were cultured in the presence of cow's milk proteins (CMP), and the release of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 4 and 6 was measured. The effect of culture supernatants was tested on HT29 cl.19A intestinal cell monolayers mounted in Ussing chambers. RESULTS: When stimulated by CMP, PBMC from infants with CMA released more TNF-alpha than those from control infants (429 +/- 92 vs. 205 +/- 34 pg/mL). Culture supernatants did not directly stimulate electrogenic chloride secretion by HT29 cl.19A cells, but epithelial barrier capacity was altered as shown by the significant decrease in electrical resistance (85 +/- 17 vs. 135 +/- 14 omega.cm2 in controls) and the increases in intact horseradish peroxidase, [14C]mannitol, and 22Na+ fluxes. These effects were reversed when culture supernatants were neutralized with anti-TNF-alpha antibodies. Recombinant human-TNF-alpha altered the HT29 cl.19A epithelial barrier capacity, and its effect was highly potentiated by IFN-gamma. CONCLUSIONS: These results indicate that during CMA, the high level of TNF-alpha released by mononuclear cells after milk protein challenge acts synergistically with IFN-gamma to increase the intestinal permeability.

Cell Line↗

PubMed1994

Modulation by interleukin-4 of cytokine release from mononuclear phagocytes in asthma.

BACKGROUND: Interleukin (IL)-4 is involved in IgE upregulation and downregulates cytokine release by mononuclear phagocytes. Mononuclear cells release greater amounts of IL-1, tumor necrosis factor-alpha, and IL-6 in patients with asthma than in control subjects, but the effect of IL-4 on cells from patients with asthma is unknown. The effects of IL-4 on the release of IL-1, tumor necrosis factor-alpha, and IL-6 by monocytes and alveolar macrophages were compared in 19 patients with asthma and 18 control subjects. METHODS: The release of IL-1, tumor necrosis factor-alpha, and IL-6 from unstimulated and lipopolysaccharide stimulated monocytes and alveolar macrophages was measured by ELISA. The effect of 30 U of IL-4 on the release of these cytokines was studied. RESULTS: Lipopolysaccharide-stimulated monocytes released significantly fewer cytokines in patients with asthma than in control subjects. IL-4 significantly inhibited cytokine release by monocytes of both groups. Unstimulated alveolar macrophages from patients with asthma released more cytokines than those of control subjects. Lipopolysaccharide induced a significantly greater increase in cytokine release in alveolar macrophages of control subjects in comparison with asthmatic subjects. IL-4 abolished the release of cytokines in alveolar macrophages from control subjects and had a minimal inhibitory effect on alveolar macrophages from patients with asthma. CONCLUSIONS: Alveolar macrophages from patients with asthma are hyperreactive but less prone to lipopolysaccharide stimulation and IL-4-downregulation than those from normal subjects.

Adolescent↗

PubMed1994

Heterogenous nitrite production by IL-4-stimulated human monocytes and peripheral blood mononuclear cells.

The capacity of human peripheral blood mononuclear cells and monocytes to generate nitrites, spontaneously or in response to Interleukin-4 was evaluated in vitro. Peripheral blood mononuclear cells and monocytes were found to release significant amounts of nitrites after 8 to 12 days in culture. This spontaneous production of nitrites was inhibited in the presence of 1 mM NG monomethyl-L-arginine, suggesting that this process was dependent upon the L-arginine metabolism. The present data also indicated that addition of Interleukin-4 generally resulted in an increased nitrite production, that was potentiated by IFN-gamma, inactive alone. The response of human monocytes to Interleukin-4 was more heterogenous than that observed with unfractionated peripheral blood mononuclear cells. These results suggest that cell/cell interactions could play an important role in the activation of the nitric oxide synthase pathway in human.

Amino Acid Oxidoreductases↗

PubMed1994

Involvement of Fc epsilon RII/CD23 and L-arginine-dependent pathway in IgE-mediated stimulation of human monocyte functions.

Elevated IgE levels are commonly observed during the inflammatory responses in allergy and a variety of infections. This Ig activates the release of multiple mediators from monocytes/macrophages. In the present work, we attempted to clarify the IgE-dependent events involved in the activation of monocyte functions. IgE-anti-IgE immune complexes induce the production of tumor necrosis factor-alpha, oxygen radicals, IL-6 and thromboxane B2 from normal human purified monocytes. Expression and cross-linkage of Fc epsilon RII/CD23 were essential for these IgE-mediated effects. Cytokine production following CD23 ligation depended on nitric oxide transduction pathway, as it was inhibited by NG-monomethyl-L-arginine, a competitive inhibitor of the conversion of L-arginine to L-citroline by nitric oxide synthase. Furthermore, addition of the nitric oxide chemical donator, Sin-1, enhanced IgE-induced monokine release. CD23-ligation also induced the production of nitrites by these cells. This work linked CD23 to the L-arginine-dependent transduction pathway and shows their involvement in IgE-mediated stimulation of human monocytes.

Arginine↗

PubMed1994

Modulation of phenotypic and functional properties of normal human mononuclear phagocytes by granulocyte-macrophage colony-stimulating factor.

In asthma, alveolar macrophages (AMs) are hyperreactive releasing large amounts of mediators and expressing high levels of surface markers. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates monocytes and AMs, and may be involved in the hyperreactivity of AMs. The effects of GM-CSF were tested on monocytes and AMs from normal subjects by examining the expression of factors thought to be upregulated in asthma. After various incubation times of GM-CSF, the expression of CD23 and beta 2-integrins (CD11a, CD11b, CD11c) was studied by FACS and the release of sCD23 was measured by ELISA. The priming and stimulatory effects of GM-CSF were tested on monocytes and AMs and the release of leukotriene B4 (LTB4) was measured by ELISA. GM-CSF induced the expression of CD11c and CD23 and the release of sCD23. GM-CSF primed and stimulated monocytes and AMs to release LTB4. The effects of GM-CSF may explain partly the hyperreactivity of AMs in asthma.

Adult↗

PubMed1994

Involvement of cyclic AMP and nitric oxide in immunoglobulin E-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes.

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast cells, macrophages, fibroblasts) during wounding, cutaneous allergy, and infections. We have previously demonstrated that after stimulation with interleukin 4 or interferon-gamma, human EK express the low-affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody induces a dose-dependent release of interleukin 6 and tumor necrosis factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, inasmuch as this is completely abolished by the use of cAMP or nitric oxide synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.

Antibodies, Monoclonal↗

PubMed1994

IgE-dependent activation of Fc epsilon RII/CD23+ normal human keratinocytes: the role of cAMP and nitric oxide.

Epidermal keratinocytes (EK) are exposed to multiple inflammatory stimuli and paracrine factors secreted by various dermal cells (lymphocytes, mast-cells, macrophages, fibroblasts) during wounding, cutaneous allergy and infections. We have previously demonstrated that following stimulation with interleukin-4 (IL-4) or interferon-gamma, human EK express the low affinity receptor for IgE (Fc epsilon RII/CD23) on their surface. In the present study, we showed that the ligation of CD23 by IgE/anti-IgE immune complexes or specific monoclonal antibody, induces a dose-dependent release of interleukin-6 and tumor necrosis factor-alpha from EK. CD23-ligation activates the nitric oxide-dependent pathway, as demonstrated by the high levels of nitrites released in cell supernatants, and the accumulation of intracellular cyclic nucleotides in EK. These second messengers are required for IgE-dependent stimulation of cytokine production by these cells, as this is completely abolished by cAMP or NO synthase antagonists. Human epithelial keratinocytes may thus participate in IgE-mediated immune responses, through their ability to express functional CD23 antigen.

Amino Acid Oxidoreductases↗

PubMed1994

[Physiopathological role of low affinity IgE receptor (CD23) in hematopoietic cells].

Ligation of the low affinity IgE receptor by specific monoclonal antibodies or multivalent IgE complexes result in the transduction of signals which differ according to the CD23 isotype expressed by the various cell types. In B lymphocytes, it elicits the early activation of phospholipase C through a mechanism involving a G-protein insensitive to Pertussis toxin, followed by a late phase of cAMP accumulation. In monocytes, which express the CD23b isoform, ligation of CD23 was also found to induce a delayed accumulation of cAMP, that was largely dependent on a prior cGMP increase through a mechanism involving the activation of a NO synthase. This pathway, which appears to be exacerbated in allergic diseases, seems to play an important role in the differentiation of cells of the monocytic lineage, their capacity to release proinflammatory mediators and their cytotoxic functions.

Amino Acid Oxidoreductases↗

PubMed1994

Regulatory role of nitric oxide in the IL-4-induced IgE production by normal human peripheral blood mononuclear cells.

An in vitro study was performed in order to assess a possible regulatory role of nitric oxide (NO), a short-lived biologic mediator that displays immunoregulatory properties, in the IL-4-driven synthesis of IgE by normal human peripheral blood mononuclear cells (PBMC). In addition to induce IgE production, IL-4 was found to elicit nitrite (NO2-) release by PBMC. A marked correlation was observed between IgE secretion and nitrite release by PBMC stimulated with an optimal concentration of IL-4. The IL-4-dependent IgE production was significantly reduced (p < 0.001) in the presence of N omega-monomethyl-L-arginine (LNMMA), an inhibitor of the NO-synthase pathway; this inhibition was partially reverted with an excess of L-arginine. Addition to PBMC cultures of the chemical NO donor Sin-1, inactive alone, was found to result, depending on the concentration of IL-4, in either potentiation (suboptimal concentration of IL-4, 10 ng/ml) or inhibition (optimal concentration of IL-4, 50 ng/ml) of IgE synthesis. The potentiating effect of Sin-1 was dose dependent, with a maximal effect for 300 microM, whereas its metabolite Sin-1c was inactive. In both cases, Sin-1 markedly reduced the IL-4-induced release of the soluble form of the low affinity IgE receptor (sCD23). Together, these data strongly suggest that NO may display biphasic immunoregulatory properties on the IL-4-induced IgE production by PBMC.

Arginine↗

PubMed1994

[Role of interleukin-4 in the regulation of nitric oxide production by normal human monocytes].

Resting normal human monocytes were found to produce small amounts of cGMP in response to IL-4. This production was inhibited in the presence of LNMMA suggesting an association with activation of the NO synthase (NOS) pathway. In addition, this cGMP generation was abrogated in the presence of either a Ca2+ chelator, EGTA, or a calcium/calmodulin inhibitor, W7, suggesting that IL-4 stimulates the constitutive NOS (cNOS). An enhanced response was observed when monocytes were preincubated with IFN-gamma and whether the cGMP accumulation was still abrogated in the presence of LNMMA it was not affected by either EGTA or W7 suggesting, in that case, the activation of an inducible NOS (iNOS). Taken together these data suggest that IL-4 could stimulate a cNOS in resting and an iNOS in the IFN-gamma-treated human monocytes, indicating that the generation of NO is highly dependent on the maturation state of these cells.

Cyclic GMP↗

PubMed1993

IL-4 release by human leukemic and activated normal basophils.

Recently, authors have addressed the ability of human basophils to produce IL-4. We report here the detection of significant serum IL-4 levels in a case of acute transformation of chronic myelogenous leukemia with a predominant basophilic cell population. Leukemic basophils were isolated from patients' PBMC and assayed for their IL-4-mRNA expression and their ability to secrete this cytokine in vitro. Leukemic basophilic cells (> 90% toluidine blue positive) but not other PBMC expressed IL-4-mRNA, contained IL-4 protein, and secreted this cytokine. These cells had a spontaneous IL-4 secretion ability, without a need for an exogenous activator. Meanwhile, IL-4 release was significantly increased following leukemic cell activation through Fc epsilon RI-ligation or by Ca2+ ionophore. IL-4 and its mRNA were also detected in leukemic basophils from three other chronic myelogenous leukemia patients with moderate basophilia (13, 14, and 23% basophils in PBMC). To confirm these data in normal human cells, we have developed a method to obtain large numbers of purified basophils from human bone marrow cell cultures. In contrast to leukemic basophils, normal cells required in vitro activation through Fc epsilon RI ligation or by Ca2+ ionophore to express and secrete IL-4. Leukemic and normal basophils secreted histamine following in vitro activation, but were negative for tryptase. These data thus demonstrate the in vivo and in vitro ability of human basophils to produce IL-4.

Basophils↗

PubMed1993

Ligation of CD23 triggers cyclic AMP generation in human B lymphocytes.

The low affinity IgE receptor CD23 may play a role in several B lymphocyte functions, such as cell activation and multiplication, Ag presentation, and IgE production. We have previously reported that ligation of the CD23 molecule with anti-CD23 mAb, or IgE-anti-IgE complexes, leads to phosphoinositide hydrolysis and calcium mobilization through the generation of Inositol (1,4,5) trisphosphate via a process involving a Pertussis toxin insensitive GTP-binding protein. In our work, we show that anti-CD23 mAb elicit an increase in cAMP concentration in human peripheral blood-derived B lymphocytes. This effect was detected both in resting and in IL-4-stimulated B cells displaying, respectively, low and high levels of CD23. Maximum cAMP accumulation was reached about 20 min after addition of the mAb. Involvement of Fc gamma RII in this process could be excluded because cAMP increase was also triggered by mAb anti-CD23 F(ab')2 fragments. Accumulation of cAMP was also observed when IgE-sensitized activated B lymphocytes were challenged with the specific hapten. Several lines of evidence indicate that the cAMP increase after CD23 ligation may result, in part, from the stimulation of phosphoinositidase C, inasmuch as it was markedly impaired by treatment with TMB-8, an inhibitor of InsP3-induced calcium release from intracytoplasmic stores and with BAPTA, an intracellular calcium chelator. Addition of GTP-gamma S to permeabilized B cells or to membrane preparations did not potentiate the effect of the mAb, suggesting that a Gs protein is not directly implicated in the generation of cAMP. Besides, cAMP accumulation is not due to the production of PG because it is not modified by indomethacin, an inhibitor of the cyclooxygenase pathway. Pretreatment of B lymphocytes with either anti-CD23 mAb or IL-4 led to autologous as well as heterologous desensitization. This negative cross-talk, at the level of cAMP, between the signaling pathways triggered by ligation of CD23 and of the IL-4 receptor, could contribute to the inhibitory effect of anti-CD23 mAb on IL-4-dependent B cell activation and differentiation.

Antibodies, Monoclonal↗

PubMed1993

Interleukin-9 potentiates the interleukin-4-induced immunoglobulin (IgG, IgM and IgE) production by normal human B lymphocytes.

IgE production by normal peripheral blood lymphocytes (PBL) is known to be triggered upon stimulation by interleukin (IL)-4. In the present study we showed that IL-9, another T cell-derived cytokine, markedly potentiated IgE production induced by suboptimal doses of IL-4, whereas no effect of IL-9 was observed in the absence of IL-4. The potentiating effect of IL-9 appeared to be associated with the increased frequency of IgE-producing cells, as revealed by a specific ELISA-spot assay. Under the same experimental conditions, IL-9 also enhanced the IL-4-induced IgG production but did not elicit IgM production. However, IL-9 did not amplify the IL-4-dependent expression of membrane-bound and soluble low affinity receptor for IgE (CD23). IL-4-induced IgE production was also potentiated by IL-6 but not by tumor necrosis factor-alpha and IL-1 beta. The possibility that the activity of IL-9 was mediated by IL-6 released from accessory cells was excluded by the observations that monocyte depletion did not abolish the effect of IL-9 and that IL-9 was still active on fluorescence-assisted cell sorted CD20+ B lymphocytes co-cultured with irradiated murine EL4 cells. In addition, IL-9 was shown to potentiate the IL-4-induced IgG and IgM production by normal human B lymphocytes preactivated with Staphylococcus aureus Cowan strain. Taken together, these data suggest that IL-9 plays a regulatory role in the IL-4-dependent immunoglobulin production.

Antibody Formation↗

PubMed1993

Intracellular signaling events associated with the induction of DNA synthesis in human B lymphocytes. I. Stimulation of PKC-dependent and -independent pathways by LMW-BCGF.

The low molecular weight B cell growth factor (LMW-BCGF) induces the G1 --> S transition in human B lymphocytes activated by a first signal, Staphylococcus aureus Cowan (SAC) or anti-mu antibody. It also stimulates proliferation of normal long-term B cell lines and some B cell tumors. We have previously reported that LMW-BCGF induces the hydrolysis of polyphosphoinositides (PI) and a rise in intracellular free calcium concentration, through the generation of inositol trisphosphate (InsP3) (Renard et al., J. Immunol. 18, 1705, 1988). In the present work we have analyzed the possible association between early signaling events elicited by LMW-BCGF in SAC-activated B cells and its ability to provoke DNA synthesis, notably at the level of phospholipase C (PLC) and protein kinase C (PK-C) activation. Inhibitors of PLC and of InsP3-induced calcium release were found to block LMW-BCGF-dependent DNA synthesis. An increase in membrane-associated protein kinase C (PK-C) activity was detected after the addition of the growth factor and the mitogenic effect of LMW-BCGF was partially suppressed when B cell blasts were incubated with staurosporine or H-3, two inhibitors of PK-C activity. In addition, the mitogenic effect due to the addition of LMW-BCGF was not modified by the incubation of B cell blasts with high concentrations of TPA, even if this treatment inhibited cellular response to a low concentration of TPA. LMW-BCGF also increased intracellular pH in B cell blasts and lymphokine-induced mitogenic activity was reduced when the Na+/H+ amiloride or ethylisopropyl amiloride (EIPA) antiport blockers were added. These results suggest that (i) LMW-BCGF-induced PI breakdown and CA2+ mobilization and cell alkalinization are associated with the induction of cell proliferation, and (ii) the activation of PK-C does not appear to be the sole pathway activated by LMW-BCGF.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1993

Intracellular signaling events associated with the induction of DNA synthesis in human B lymphocytes. II. Different pathways triggered by IL-2 and IL-4.

In attempts to detect associations between early signaling events triggered by interleukins and the induction of DNA synthesis, inhibitors of various second messenger pathways were tested for their effects on IL-2- and IL-4-elicited mitogenesis in preactivated human B lymphocytes. Inhibitors of phosphoinositidase C and of InsP3-induced calcium release suppressed IL-4- but not IL-2-mediated proliferation. The response to both lymphokines was also impaired by an inhibitor of the calcium/calmodulin complex and was modulated by variations of the [Ca2+]i. PKC inhibitors and PK-C depletion did not significantly alter the response to IL-2 and IL-4. The response to IL-2, but not to IL-4, was inhibited by cAMP analogues or by agents that raise cAMP. In contrast, IL-4, but not IL-2, stimulated cAMP accumulation in activated B cells. Taken together, these observations indicate that IL-2 and IL-4 use different signaling pathways to induce the G1-->S transition in these cells and suggest that the IL-4 inhibition of the B cell response to IL-2 may result from its effect on cAMP generation.

B-Lymphocytes↗