The imbalance between Bim and Mcl-1 expression controls the survival of human myeloma cells.


:Multiple myeloma is a fatal B cell malignancy characterized by the accumulation of plasma cells within the bone marrow. IL-6 is a major survival factor for myeloma cells. Bcl-2 protein family regulates pathways to apoptosis that are activated upon growth factor deprivation. Pro-apoptotic proteins that have only a single Bcl-2 homology domain, BH3-only, are potent inducers of apoptosis. In myeloma cells, Mcl-1 has been shown to be a major anti-apoptotic protein that appears to regulate cell survival through the JAK/STAT pathway. In this study, we examined the regulation of the BH3-only protein Bim and its interaction with Mcl-1. The three major Bim isoforms are expressed in myeloma cells and are negatively regulated by IL-6. Blockade of IL-6 signaling induces an up-regulation of Bim concomitant to Mcl-1 down-regulation. Of major interest, Bim is found strongly associated with Mcl-1 in viable myeloma cells while this interaction is disrupted under apoptosis induction. Of note, while Bim is also found strongly associated to Bcl-2, this interaction is not changed under apoptosis induction. Thus, in myeloma cells, Mcl-1 neutralizes Bim through complex formation and therefore prevents apoptosis. Under apoptosis induction, the disappearance of Mcl-1 allows Bim to exercise its pro-apoptotic function and to activate Bax.


Eur J Immunol


Gomez-Bougie P,Bataille R,Amiot M





Has Abstract


2004-11-01 00:00:00












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    abstract::The magnitude of the output of lymphocytes from Peyer's patches (PP), the morphology of the lymphocytes and their route of exit from PP has been examined in sheep. An extracorporeal perfusion system was used to selectively label a 3-4 m length of the terminal ileum of lambs at 6-10 weeks of age (the mesenteric lymph n...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Reynolds JD,Pabst R

    更新日期:1984-01-01 00:00:00

  • A novel IL-23p19/Ebi3 (IL-39) cytokine mediates inflammation in Lupus-like mice.

    abstract::Interleukin-12 family cytokines have emerged as critical regulators of immunity with some members (IL-12, IL-23) associated with disease pathogenesis while others (IL-27, IL-35) mitigate autoimmune diseases. Each IL-12 family member is comprised of an α and a β chain, and chain-sharing is a key feature. Although four ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Wang X,Wei Y,Xiao H,Liu X,Zhang Y,Han G,Chen G,Hou C,Ma N,Shen B,Li Y,Egwuagu CE,Wang R

    更新日期:2016-06-01 00:00:00

  • Transient depletion of T cells with high LFA-1 expression from peripheral circulation during acute Plasmodium falciparum malaria.

    abstract::Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area of Sudan were analyzed for...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Hviid L,Theander TG,Abdulhadi NH,Abu-Zeid YA,Bayoumi RA,Jensen JB

    更新日期:1991-05-01 00:00:00

  • An alternative pathway of B cell activation: stilbene disulfonates interact with a Cl- binding motif on AEn-related proteins to stimulate mitogenesis.

    abstract::Stilbene disulfonates are known to competitively inhibit Cl-/HCO3- flux through Band 3-related anion exchange (AE) proteins. To study the role of AE in lymphocyte activation, stilbene disulfonates were added to cultures of rat splenocytes (SPL). Four different stilbene derivatives were tested and each directly stimula...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Deane KH,Mannie MD

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  • Signaling through human killer cell activating receptors triggers tyrosine phosphorylation of an associated protein complex.

    abstract::Our understanding of the biology of human natural killer (NK) cells has significantly advanced in recent years upon identification of a family of NK cell-expressed genes that encode killer cell inhibitory receptors (KIR). Individual KIR can selectively bind various HLA class I allotypes and consequently transduce inhi...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Campbell KS,Cella M,Carretero M,López-Botet M,Colonna M

    更新日期:1998-02-01 00:00:00

  • The nylon wool adherence marker of the B cell lineage appears at the resting pre-B cell stage.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Deslauriers-Boisvert N,Mercier G,Lafleur L

    更新日期:1982-04-01 00:00:00

  • Functional CD1a is stabilized by exogenous lipids.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Manolova V,Kistowska M,Paoletti S,Baltariu GM,Bausinger H,Hanau D,Mori L,De Libero G

    更新日期:2006-05-01 00:00:00

  • New simplified molecular design for functional T cell receptor.

    abstract::We have produced a chimeric single-chain T cell receptor (TcR) that combines the specific antibody recognition function and TcR/CD3 signaling properties within the same polypeptide chain. This hybrid molecule consisted of a single-chain antibody combining site that was connected over a short spacer to the transmembran...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Brocker T,Peter A,Traunecker A,Karjalainen K

    更新日期:1993-07-01 00:00:00

  • Inhibition of B cell proliferation with anti-CD19 monoclonal antibodies: anti-CD19 antibodies do not interfere with early signaling events triggered by anti-IgM or interleukin 4.

    abstract::The 95-kDa antigen recognized by the anti-CD19 panel of monoclonal antibodies is found on the surface of most cells of the B cell lineage. Anti-CD19 antibodies inhibit B cell proliferation in response to anti-Ig plus interleukin 4 (IL4), but enhance the response to mitogenic concentrations of either phorbol 12-myrista...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Rigley KP,Callard RE

    更新日期:1991-03-01 00:00:00

  • Differential effects of the tryptophan metabolite 3-hydroxyanthranilic acid on the proliferation of human CD8+ T cells induced by TCR triggering or homeostatic cytokines.

    abstract::Production of indoleamine 2,3-dioxygenase (IDO) by tumor cells, leading to tryptophan depletion and production of immunosuppressive metabolites, may facilitate immune tolerance of cancer. IDO gene is also expressed in dendritic cells (DC) upon maturation induced by lipopolysaccarides or IFN. We investigated IDO gene e...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Weber WP,Feder-Mengus C,Chiarugi A,Rosenthal R,Reschner A,Schumacher R,Zajac P,Misteli H,Frey DM,Oertli D,Heberer M,Spagnoli GC

    更新日期:2006-02-01 00:00:00

  • α-Galactosylceramide-activated murine NK1.1(+) invariant-NKT cells in the myometrium induce miscarriages in mice.

    abstract::Innate immunity, which is unable to discriminate self from allo-antigens, is thought to be important players in the induction of miscarriages. Here, we show that the administration of IL-12 to syngeneic-mated C57BL/6 mice on gestation day 7.5 (Gd 7.5), drives significant miscarriages in pregnant females. Furthermore, ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Ichikawa T,Negishi Y,Shimizu M,Takeshita T,Takahashi H

    更新日期:2016-08-01 00:00:00

  • Autoimmune diseases linked to abnormal K+ channel expression in double-negative CD4-CD8- T cells.

    abstract::Using the patch-clamp technique in combination with fluorescence microscopy we have found an abnormality in voltage-gated K+ channel expression in T cells that represents the first molecular marker linking three disparate autoimmune diseases in mice. CD4-CD8-Thy-1.2+ (double-negative or DN) lymphocytes from every know...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Chandy KG,Cahalan MD,Grissmer S

    更新日期:1990-04-01 00:00:00

  • Flt3 ligand improves the innate response to respiratory syncytial virus and limits lung disease upon RSV reexposure in neonate mice.

    abstract::Respiratory syncytial virus (RSV) causes severe bronchiolitis in infants worldwide. The immunological factors responsible for RSV susceptibility in infants are poorly understood. Here, we used the BALB/c mouse model of neonatal RSV infection to study the mechanisms leading to severe disease upon reexposure to the viru...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Remot A,Descamps D,Jouneau L,Laubreton D,Dubuquoy C,Bouet S,Lecardonnel J,Rebours E,Petit-Camurdan A,Riffault S

    更新日期:2016-04-01 00:00:00

  • Direct helper T cell-induced B cell differentiation involves interaction between T cell antigen CD28 and B cell activation antigen B7.

    abstract::Cognate interactions between major histocompatibility complex class II antigen (Ag)-reactive CD4+ T helper (Th) and Ag-presenting B cells induce first the activation of B cells and their subsequent differentiation into Ig-secreting cells (IgSC). The Th cell-associated homodimeric glycoprotein CD28 has been implicated ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Damle NK,Linsley PS,Ledbetter JA

    更新日期:1991-05-01 00:00:00

  • Physiology of murine B lymphocytes. I. Life-spans of anti-mu and haptenated Ficoll (thymus-independent antigen)-reactive B cells.

    abstract::We have evaluated the life-span of B lymphocytes by measuring the functional reactivity of normal B cells upon transfer into xid mice, which do not respond to anti-mu, fluoresceinated-Ficoll (FL-Ficoll) and 2,4,6-trinitrophenyl aminoethylcarbamylmethyl Ficoll (TNP-Ficoll). After 4 days of transfer only 30-40% of anti-...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Udhayakumar V,Goud SN,Subbarao B

    更新日期:1988-10-01 00:00:00

  • A critical role for p59(fyn) in CD2-based signal transduction.

    abstract::TCR- but not CD2-triggered IL-2 production is p56(lck) dependent. To test the hypothesis that p59(fyn), a second src-family protein tyrosine kinase (PTK) expressed in T lymphocytes, might be an essential upstream component of the CD2 signaling pathway, we generated human (h) CD2 transgenic (tg) fyn(+/+) and fyn(-/-) m...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Fukai I,Hussey RE,Sunder-Plassmann R,Reinherz EL

    更新日期:2000-12-01 00:00:00

  • Coupling of antigen to cholera toxin for dendritic cell vaccination promotes the induction of MHC class I-restricted cytotoxic T cells and the rejection of a cognate antigen-expressing model tumor.

    abstract::We previously demonstrated that cholera toxin (CT) is highly efficient as a combined carrier and adjuvant for dendritic cell (DC) vaccination, inducing strong Th1-dominated B cell and CD4(+) T cell responses. In this study we show that vaccination with DC pre-pulsed ex vivo with CT-conjugated OVA (OVA-CT) gives rise t...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Eriksson K,Sun JB,Nordström I,Fredriksson M,Lindblad M,Li BL,Holmgren J

    更新日期:2004-05-01 00:00:00

  • Therapeutic targeting of alpha 4-integrins in chronic inflammatory diseases: tipping the scales of risk towards benefit?

    abstract::Inhibition of leukocyte trafficking via alpha4-integrin antibody blockade has recently become a validated therapeutic approach for several inflammatory diseases, including multiple sclerosis, ulcerative colitis and Crohn's disease. In the midst of this recent success, 3 patients receiving chronic treatment with the an...

    journal_title:European journal of immunology

    pub_type: 杂志文章,评审


    authors: Engelhardt B,Briskin MJ

    更新日期:2005-08-01 00:00:00

  • Guinea pig immunoglobulin light chain isotypes. II. The preferential expression of lambda chain-bearing anti-phenyltrimethylammonium antibodies is associated with restricted variable region expression, but not with any alteration in the proportion of lamb

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Brunhouse RF,Cebra JJ

    更新日期:1978-12-01 00:00:00

  • Immuno-electron microscopic characterization of large granular lymphocytes (natural killer cells) from rat liver.

    abstract::The immunocytochemical characteristics of large granular lymphocytes (LGL), isolated from the liver sinusoids of euthymic and athymic (nude) rats, were investigated in electron microscopy by the immunoperoxidase technique. The LGL were found positive for MRC OX-8 (natural killer cells and cytotoxic/suppressor T cells)...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Bouwens L,Wisse E

    更新日期:1987-10-01 00:00:00

  • CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation.

    abstract::A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key role in T cell-dependent B cell stimulation. CD8+ T cell clones were examined for CD40L expression and for their capacity to allow the growth and differentiation of B cells, upon activation with immobilized anti-CD3. Accord...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Hermann P,Van-Kooten C,Gaillard C,Banchereau J,Blanchard D

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  • The gene expression profile of phosphoantigen-specific human γδ T lymphocytes is a blend of αβ T-cell and NK-cell signatures.

    abstract::Global transcriptional technologies have revolutionised the study of lymphoid cell populations, but human γδ T lymphocytes specific for phosphoantigens remain far less deeply characterised by these methods despite the great therapeutic potential of these cells. Here we analyse the transcriptome of circulating TCRVγ(+)...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Pont F,Familiades J,Déjean S,Fruchon S,Cendron D,Poupot M,Poupot R,L'faqihi-Olive F,Prade N,Ycart B,Fournié JJ

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Sartoris S,Tosi G,De Lerma Barbaro A,Cestari T,Accolla RS

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  • Misinitiation of intrathymic MART-1 transcription and biased TCR usage explain the high frequency of MART-1-specific T cells.

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    更新日期:2014-09-01 00:00:00

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Madonna S,Scarponi C,Doti N,Carbone T,Cavani A,Scognamiglio PL,Marasco D,Albanesi C

    更新日期:2013-07-01 00:00:00

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Vangsted A,Neisig A,Wallin H,Zeuthen J,Geisler C

    更新日期:1993-06-01 00:00:00

  • Differential impact of the transcriptional repressor Gfi1 on mature CD4+ and CD8+ T lymphocyte function.

    abstract::The transcriptional repressor Gfi1 is a nuclear zinc-finger protein that is expressed in T cell precursors in the thymus, but is down-regulated in mature, resting T cells. Gfi1 expression rises transiently to levels seen in thymocytes upon antigenic activation. We show here that lack of Gfi1 causes delayed cell cycle ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Pargmann D,Yücel R,Kosan C,Saba I,Klein-Hitpass L,Schimmer S,Heyd F,Dittmer U,Möröy T

    更新日期:2007-12-01 00:00:00

  • Maternal-fetal tolerance is maintained despite transgene-driven trophoblast expression of MHC class I, and defects in Fas and its ligand.

    abstract::During mammalian pregnancy, one or more semiallogeneic fetuses gestate in direct contact with the maternal circulation and uterine tissue. However, a damaging maternal immune response is not normally provoked. We studied two possible mechanisms for this maternal-fetal tolerance, alone and in combination. First, we dir...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Rogers AM,Boime I,Connolly J,Cook JR,Russell JH

    更新日期:1998-11-01 00:00:00

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    journal_title:European journal of immunology

    pub_type: 评论,杂志文章,评审


    authors: Graça L,Silva-Santos B,Coutinho A

    更新日期:2006-04-01 00:00:00

  • Localization of the site of the IgG molecule that regulates maternofetal transmission in mice.

    abstract::Site-directed mutagenesis of a recombinant Fc hinge fragment has recently been used to localize the site of the mouse IgG1 (mIgG1) molecule that is involved in the intestinal transfer of recombinant Fc hinge fragments in neonatal mice. This site encompasses Ile-253, His-310, Gln-311, His-433 and Asn-434, localized at ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Medesan C,Radu C,Kim JK,Ghetie V,Ward ES

    更新日期:1996-10-01 00:00:00