Binding of nucleosomes to a cell surface receptor: redistribution and endocytosis in the presence of lupus antibodies.


:In the present study, we sought evidence for a surface nucleosome receptor in the fibroblastic cell line CV-1, and questioned whether anti-double-stranded (ds) DNA and/or anti-histone autoantibodies could recognize and influence the fate of cell surface-bound nucleosomes. 125I-labeled mononucleosomes were shown to bind to the cell layer in a specific, concentration-dependent and a saturable manner. Scatchard analysis revealed the presence of two binding sites: a high-affinity site with a Kd of approximately 7nM and a low-affinity site (Kd approximately 400 nM) with a high capacity of 9 x 10(7) sites. Visualization of bound mononucleosomes by fluorescence revealed staining on both the cell surface and the extracellular matrix (ECM). Purified mononucleosome-derived ds DNA (180-200 bp) was found to complete for binding of 125I-mononucleosomes on the low-affinity site, to stain exclusively the ECM in immunofluorescence, and to precipitate three specific proteins of 43, 180 and 240 kDa from 125-I-labeled cell lysates. Nucleosomes were found to precipitate not only the 180-kDa ds DNA-reactive component, but also a unique protein of 50 kDa, suggesting that this protein is a cell surface receptor for nucleosomes on these fibroblasts. Once bound on the cell surface, mononucleosomes were recognized and secondarily complexed by lupus anti-ds DNA or anti-histone antibodies (i.e. anti-nucleosome antibodies), thus forming immune complexes in situ. The presence of these complexing auto-antibodies was found dramatically to enhance the kinetics of mononucleosome internalization. Following the internalization of the nucleosome-anti-nucleosome complexes by immunofluorescence, we observed the formation of vesicles at the edge of the cells by 5-10 min which moved toward the perinuclear region by 20-30 min. By means of double-fluorescence labeling and proteolytic treatment, these fluorescent vesicles were shown to be in the cytoplasm, suggesting true endocytosis of nucleosome-anti-nucleosome immune complexes. As shown by confocal microscopy, at no stage of this endocytic process was there any indication that coated pits or coated vesicles participated. Co-distribution of the endocytic vesicles with regions rich in actin filaments and inhibition of endocytosis of nucleosome-anti-nucleosome complexes by disruption of the microfilament network with cytochalasin D suggest a mechanism mediated by the cytoskeleton. Taken together, our data provide evidence for the presence of a surface nucleosome receptor. We also show that anti-ds DNA and anti-histone antibodies can form nucleosome-anti-nucleosome immune complexes in situ at the cell surface, and thus dramatically enhance the kinetics of nucleosome endocytosis.


Eur J Immunol


Koutouzov S,Cabrespines A,Amoura Z,Chabre H,Lotton C,Bach JF




Has Abstract


1996-02-01 00:00:00












  • Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis.

    abstract::In the homeostasis of the immune system regulatory cells play a major role. Removal of one group of regulatory cells, the CD25(+)CD4(+) T cells, leads to autoimmune manifestations in experimental animal models, and reintroduction of this population prevents disease. This study addresses the role of such regulatory T c...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Cao D,Malmström V,Baecher-Allan C,Hafler D,Klareskog L,Trollmo C

    更新日期:2003-01-01 00:00:00

  • Recombinant cytomegalovirus glycoprotein gB (UL55) induces an autoantibody response to the U1-70 kDa small nuclear ribonucleoprotein.

    abstract::Human cytomegalovirus (CMV) infection can be life threatening in the immune compromised and is associated with congenital defects and / or mental retardation in the neonate. The demonstrated association between CMV infection and rheumatoid factor (RF) raised the possibility of an induction of an autoimmune response up...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Curtis HA,Singh T,Newkirk MM

    更新日期:1999-11-01 00:00:00

  • Hhex regulates murine lymphoid progenitor survival independently of Stat5 and Cdkn2a.

    abstract::The transcription factor Hhex (hematopoietically expressed homeobox gene) is critical for development of multiple lymphoid lineages beyond the common lymphoid progenitor. In addition, Hhex regulates hematopoietic stem cell (HSC) self-renewal, emergency hematopoiesis, and acute myeloid leukemia initiation and maintenan...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Jackson JT,O'Donnell K,Light A,Goh W,Huntington ND,Tarlinton DM,McCormack MP

    更新日期:2020-07-01 00:00:00

  • ME3738 protects from concanavalin A-induced liver failure via an IL-6-dependent mechanism.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Klein C,Wüstefeld T,Heinrich PC,Streetz KL,Manns MP,Trautwein C

    更新日期:2003-08-01 00:00:00

  • Activation rather than Foxp3 expression determines that TGF-β-induced regulatory T cells out-compete naïve T cells in dendritic cell clustering.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Chen Y,Adams E,Regateiro FS,Vaux DJ,Betz AG,Andersen KG,Waldmann H,Howie D

    更新日期:2012-06-01 00:00:00

  • The emigration of lymphocytes from Peyer's patches in sheep.

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    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

  • Influence of maternal antibodies on vaccine responses: inhibition of antibody but not T cell responses allows successful early prime-boost strategies in mice.

    abstract::The transfer of maternal antibodies to the offspring and their inhibitory effects on active infant immunization is an important factor hampering the use of certain vaccines, such as measles or respiratory syncytial virus vaccine, in early infancy. The resulting delay in protection by conventional or novel vaccines may...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Siegrist CA,Barrios C,Martinez X,Brandt C,Berney M,Córdova M,Kovarik J,Lambert PH

    更新日期:1998-12-01 00:00:00

  • Lack of somatic mutation in a kappa light chain transgene.

    abstract::Analysis of mice transgenic for immunoglobulin genes should allow definition of the cis-acting DNA sequences required to target somatic mutation to antibody V genes. We have looked for mutations in a chimeric kappa transgene encoding a V region specific for the hapten 2-phenyloxazolone (phOx) linked to a rat C kappa g...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Sharpe MJ,Neuberger M,Pannell R,Surani MA,Milstein C

    更新日期:1990-06-01 00:00:00

  • Multifocal structure of the T cell - dendritic cell synapse.

    abstract::The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Brossard C,Feuillet V,Schmitt A,Randriamampita C,Romao M,Raposo G,Trautmann A

    更新日期:2005-06-01 00:00:00

  • Augmentation of major histocompatibility complex class I and ICAM-1 expression on glial cells following measles virus infection: evidence for the role of type-1 interferon.

    abstract::An intracellular staining procedure for the cytoskeletal marker, glial fibrillary acidic protein of astrocytes, has been developed which allows flow cytometric phenotyping of astrocytes within complex mixtures of glial cells. Employing this technique, we show here that measles virus infection of rat mixed glial cell c...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Kraus E,Schneider-Schaulies S,Miyasaka M,Tamatani T,Sedgwick J

    更新日期:1992-01-01 00:00:00

  • The NF-κB regulator Bcl-3 modulates inflammation during contact hypersensitivity reactions in radioresistant cells.

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    authors: Tassi I,Rikhi N,Claudio E,Wang H,Tang W,Ha HL,Saret S,Kaplan DH,Siebenlist U

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  • Cyclophilin A is required for M-CSF-dependent macrophage proliferation.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Sànchez-Tilló E,Wojciechowska M,Comalada M,Farrera C,Lloberas J,Celada A

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  • Treg suppress CTL responses upon immunization with HSP gp96.

    abstract::HSP gp96-based vaccines have been trialled in rodent models and, more recently, in humans. Better understanding of gp96's immunomodulatory role will help with the design of more effective strategies for treatment of cancer and infectious diseases. In this study, we monitored the activities of T cells and activation of...

    journal_title:European journal of immunology

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    authors: Liu Z,Li X,Qiu L,Zhang X,Chen L,Cao S,Wang F,Meng S

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  • Polyclonal Treg cells modulate T effector cell trafficking.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Davidson TS,Shevach EM

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  • An HLA-B35-restricted epitope modified at an anchor residue results in an antagonist peptide.

    abstract::Peptides associated with HLA-B35 commonly have a proline or occasionally a serine residue in the P2 anchor position of the peptide, with a tyrosine at the C terminus. Based on this motif, we identified an octamer epitope from influenza A matrix protein which is presented by HLA-B35. The requirements for MHC binding an...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Dong T,Boyd D,Rosenberg W,Alp N,Takiguchi M,McMichael A,Rowland-Jones S

    更新日期:1996-02-01 00:00:00

  • Proteins in normal and malignant cells, cross-reacting with the latent membrane protein encoded by Epstein-Barr virus.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Hatzubai A,Lerner RA,Klein G,Sulitzeanu D

    更新日期:1988-08-01 00:00:00

  • Human basophils release interleukin-4 after stimulation with Schistosoma mansoni egg antigen.

    abstract::The elevated interleukin (IL)-4 and IgE production in Schistosoma mansoni infection seems to be induced essentially by the egg stage of the parasite. The underlying mechanism, however, is not known. Since basophils from human peripheral blood can produce IL-4, we asked, whether soluble S. mansoni egg antigens (SEA) wo...

    journal_title:European journal of immunology

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    authors: Falcone FH,Dahinden CA,Gibbs BF,Noll T,Amon U,Hebestreit H,Abrahamsen O,Klaucke J,Schlaak M,Haas H

    更新日期:1996-05-01 00:00:00

  • IL-10 interrupts memory B cell expansion in the germinal center by inducing differentiation into plasma cells.

    abstract::Germinal center (GC) B cells undergo proliferation, somatic hypermutation and isotype switching in the course of differentiation into plasma cells to produce high-affinity antibodies. To understand the molecular mechanism regulating the expansion of memory B cells and the termination of expansion by differentiation in...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Choe J,Choi YS

    更新日期:1998-02-01 00:00:00

  • Genetic control of B cell function. III. IgVH-controlled polymorphism in the frequencies of B cells that recognize xenogeneic red blood cells.

    abstract::Previous work has shown that the primary IgM plaque-forming cell response of inbred mice to xenogeneic red blood cells (RBC) including sheep, horse and chicken RBC is under the control of two polymorphic genes or sets of genes, one linked to the Igh linkage group and the other of unknown linkage but unlinked to H-2 an...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Saizawa KM,Melchers I,Eichmann K

    更新日期:1985-02-01 00:00:00

  • Rapid IgE desensitization is antigen specific and impairs early and late mast cell responses targeting FcεRI internalization.

    abstract::Rapid IgE desensitization provides temporary tolerization for patients who have presented severe hypersensitivity reactions to food and drugs, protecting them from anaphylaxis, but the underlying mechanisms are still incompletely understood. Thus, here we develop an effective and reproducible in vitro model of rapid I...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Sancho-Serra Mdel C,Simarro M,Castells M

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  • T cells generated in the absence of a thoracic thymus fail to establish homeostasis.

    abstract::Cervical thymus mimics the thoracic thymus in supporting T-cell development and exists in a subset of mice and humans. Importantly, it remains unknown whether the cervical thymus can generate T cells that are self-tolerant in the complete absence of signals from the thoracic thymus. Using a fetal liver reconstitution ...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Smolarchuk C,Zhu LF,Chan WF,Anderson CC

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  • Disruption of de novo fatty acid synthesis via acetyl-CoA carboxylase 1 inhibition prevents acute graft-versus-host disease.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Raha S,Raud B,Oberdörfer L,Castro CN,Schreder A,Freitag J,Longerich T,Lochner M,Sparwasser T,Berod L,Koenecke C,Prinz I

    更新日期:2016-09-01 00:00:00

  • Epratuzumab modulates B-cell signaling without affecting B-cell numbers or B-cell functions in a mouse model with humanized CD22.

    abstract::Treatment of systemic lupus erythematosus patients with epratuzumab (Emab), a humanized monoclonal antibody targeting CD22, leads to moderately reduced B-cell numbers but does not completely deplete B cells. Emab appears to induce immunomodulation of B cells, but the exact mode of action has not been defined. In the p...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Özgör L,Brandl C,Shock A,Nitschke L

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  • Evidence for the stochastic acquisition of cytokine profile by CD4+ T cells activated in a T helper type 2-like response in vivo.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Kelso A,Groves P,Troutt AB,Francis K

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  • TLR activation of tumor-associated macrophages from ovarian cancer patients triggers cytolytic activity of NK cells.

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    journal_title:European journal of immunology

    pub_type: 临床试验,杂志文章


    authors: Bellora F,Castriconi R,Dondero A,Pessino A,Nencioni A,Liggieri G,Moretta L,Mantovani A,Moretta A,Bottino C

    更新日期:2014-06-01 00:00:00

  • New insights into the subversion of the chemokine system by poxviruses.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Alcami A

    更新日期:2007-04-01 00:00:00

  • Differential requirement for CARMA1 in agonist-selected T-cell development.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Medoff BD,Sandall BP,Landry A,Nagahama K,Mizoguchi A,Luster AD,Xavier RJ

    更新日期:2009-01-01 00:00:00

  • CD4+CD25+ T cells as immunoregulatory T cells in vitro.

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Chai JG,Tsang JY,Lechler R,Simpson E,Dyson J,Scott D

    更新日期:2002-08-01 00:00:00

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    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Hontebeyrie-Joskowicz M,Said G,Milon G,Marchal G,Eisen H

    更新日期:1987-07-01 00:00:00

  • Conserved distribution of lambda subtypes from rearranged gene segments to immunoglobulin synthesis in the mouse B cell repertoire.

    abstract::The immunoglobulin lambda light chain system displays a limited diversity in inbred mice. Indeed, the lambda locus is organized in two recombination units: V lambda 2-V lambda x-J lambda 2-C lambda 2-psi J lambda 4-psi C lambda 4, which can produce either lambda 2(V2) or lambda 2(Vx) chains; and V lambda 1-J lambda 3-...

    journal_title:European journal of immunology

    pub_type: 杂志文章


    authors: Boudinot P,Drapier AM,Cazenave PA,Sanchez P

    更新日期:1994-09-01 00:00:00