Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell precursors.

Pandrau, D.; Saeland, Sem; Duvert, V; Durand, Isabelle; Manel, Anne‐Marie; Zabot, Marie Thérèse; Philippe, N; Banchereau, Jacques

doi:10.1172/jci116042

Cited by 29 publications

(13 citation statements)

References 32 publications

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“…Either in mice or humans, various cytokines have been suggested to play some role in precursor B cell growth or differentiation. These include IL-2 [21], IL-3 [22], IL-4 [23] and IL-7 [24-271. There is a body of evidence supporting the essential role of IL-7 in promoting mouse precursor B cell growth .…”

Section: Discussionmentioning

confidence: 99%

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis

Lévy¹,

Benlagha²,

Buzyn³

et al. 1997

Clinical and Experimental Immunology

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SUMMARYHomeostasis of human B cell development is maintained by a complex network of cytoplasmic and surface expressed molecules. Abnormalities in this process may result in the expansion of malignant B cell precursors in B lineage acute lymphoblastic leukaemia (ALL). ALL cells share surface antigens with normal early precursor B cells. We have studied here the role of Fas/APO-1 (CD95) antigen on leukaemic precursor B cell line growth and survival, and the modulation of its effects by signals involved in normal early B cell development. Four ALL cell lines representative of the early steps of B cell differentiation are shown to express surface Fas/APO-1 (CD95) antigen and to undergo apoptosis in the presence of anti-Fas cross-linking antibodies. This effect is strongly enhanced when pre-B, but not pro-B cells, are pretreated with IL-7 but not with IL-2, IL-3, IL-4 or IL-10. Furthermore, pre-B cell death induced by anti-Fas antibodies in combination with IL-7 is increased upon pre-B receptor but not CD19 cross-linking. Bcl-2 and Bax protein expression is not influenced by IL-7 or pre-BR stimulation in either pro-B or pre-B cell lines. These results indicate that signals involved in normal early B cell development can modulate the Fas (CD95)-mediated apoptosis of leukaemic precursor B cells.

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Section: Discussionmentioning

confidence: 99%

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis

Lévy¹,

Benlagha²,

Buzyn³

et al. 1997

Clinical and Experimental Immunology

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“…B lineage acute lymphoblastic leukemia cell lines pre-ALP and Dunatis were produced in our laboratory [13,141; EBVtransformed cell lines produced in the laboratory were: 61,3,7, Bm2'b CD38+, IgD', IgM-displaying VH3(61), VH4(63) and VH5(67) specificities (C. Arpin, 0. de Bouteiller, D. Razanajaona et al, submitted); yl, 2, 3, 5, 6, CD38+, IgD-germinal center (GC)-derived B cells (C. Arpin, 0. de Bouteiller, D. Razanajaona et al, submitted); and G27E9 (BAB4), GllA9 (BAB2) [15], M4, producing respectively IgG2, IgG4 and IgG3; Gus no. 50 a Tcell hybridoma.…”

Section: Cell Lines and Preparationsmentioning

confidence: 99%

Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells

Bates¹,

Ravel²,

Dieu³

et al. 1997

Eur J Immunol

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Using a cDNA subtraction technique, a novel member of the ubiquitin family was isolated from human dendritic cells. This gene encodes a diubiquitin protein containing tandem head to tail ubiquitin-like domains, with the conservation of key functional residues. Expression of this 777-bp mRNA was restricted to dendritic cells and B cells, with strong expression in mature B cells. Southern blot analysis indicated that a single copy of this gene is present. In situ hybridization on tonsillar tissue showed expression in epithelial cells and isolated cells within the germinal center. With respect to an expressed-sequence tag (EST) this cDNA could be localized to the major histocompatibility complex class I region of chromosome 6. Comparative analysis and the expression pattern of this gene suggests a function in antigen processing and presentation.

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“…At this point we do not know the exact physiologic relevance of the IL-4-induced PI 3-kinase (p85) dephosphorylation. But based on previous reports showing tyrosine phosphorylation of PI 3-kinase (p85) by growth factors such as platelet-derived growth factor and insulin (31,32), it is possible that the IL-4-induced inhibition of leukemic and normal B cell proliferation (27) may be due to the IL-4-induced PI 3-kinase (p85) dephosphorylation. Alternatively, based on our preliminary results showing that Na 3 VO 4 , a potent protein-tyrosine phosphatase inhibitor, could block the IL-4-induced IgE germline transcript expression, 2 it is tempting to speculate that protein tyrosine dephosphorylation may be necessary for the IL-4-induced signaling that leads to IgE class switching in human B cells.…”

Section: Shp-1 Associates With the Il-4r As Well As With Pi 3-kinase mentioning

confidence: 99%

Interleukin-4 (IL-4) Induces Phosphatidylinositol 3-Kinase (p85) Dephosphorylation

Imani

Rager

Catipovic

et al. 1997

Journal of Biological Chemistry

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Interleukin 4 (IL-4) is a potent cytokine produced by T cells and to a lesser extent by tumor-associated natural killer cells, basophils, and mast cells. IL-4 treatment of T cells and macrophages leads to augmentation of their cytotoxic activity. In human B cells, IL-4 is a potent stimulator of Ig class switching from IgM to IgE. The diverse biological responses induced by IL-4 are mediated through a high affinity receptor complex (IL-4R).Although a wealth of information has accumulated regarding IL-4R, the exact mechanisms of IL-4R-mediated signaling pathways in human B cells are not well defined. In an attempt to characterize the IL-4-induced signals in human B cells, we have found that IL-4 treatment induced rapid dephosphorylation of the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase. To identify the protein-tyrosine phosphatase involved in the IL-4-mediated dephosphorylation, we performed Western blot analysis using monoclonal antibodies specific to protein-tyrosine phosphatases. Upon IL-4 treatment, SHP-1 was specifically translocated to the cellular membrane fraction. Furthermore, immunoprecipitation studies revealed that SHP-1 could be specifically coimmunoprecipitated with the IL-4R as well as with phosphatidylinositol 3-kinase (p85). Collectively, our observations suggest that in addition to protein phosphorylation, protein tyrosine dephosphorylation may play a role in the IL-4-induced signaling pathways. IL-41 is a potent cytokine with pleiotropic effects on many cell types. The biological effects of IL-4 include induction of IgE class switching, induction of proliferation in T and B cells, and up-regulation of CD23 and major histocompatibility complex class II molecules on human B cells (1-4).The IL-4 receptor complex is present on many hematopoietic and non-hematopoietic cell lines (5). Although many members of the cytokine receptor family, including the IL-4 receptor (IL-4R), lack protein kinase consensus domains, ligand binding to these receptors results in tyrosine phosphorylation as well as dephosphorylation and subsequent biological responses (6, 7).Early studies of Morla et al. (8) reveal IL-4-induced tyrosine phosphorylation of proteins of 110 and 170 kDa in a murine mast cell line, IC 2.9. Subsequently, Wang et al. (9) reported IL-4-induced tyrosine phosphorylation of a 170-kDa polypeptide, termed 4PS in murine myeloid cell lines. Keegan et al. (10) reported that 4PS may be antigenically and functionally similar to the insulin receptor substrate-1. Additional evidence of IL-4-induced signal transduction events was demonstrated by the IL-4-induced association of the 85-kDa subunit of phosphatidylinositol 3-kinase (p85) with the phosphorylated form of 4PS; however, p85 itself was not phosphorylated (11).Further studies have shown that IL-4 treatment induces the association of IL-4R with the ␥ chain of the IL-2 receptor complex (12) that participates in IL-4-mediated signaling by ␥ chain-associated JAK kinases (13,14). However, experiments by He and Malek (15) provide evidence f...

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Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell precursors.

Abstract: In the present study, we have investigated the effects of IL4 on the proliferation and differentiation of leukemic and normal human B cell precursors (BCP). We have demonstrated that

Cited by 29 publications

References 32 publications

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis

IL-7 sensitizes human pre-B cells but not pro-B cells to Fas/APO-1 (CD95)-mediated apoptosis

Identification and analysis of a novel member of the ubiquitin family expressed in dendritic cells and mature B cells

Interleukin-4 (IL-4) Induces Phosphatidylinositol 3-Kinase (p85) Dephosphorylation

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