Lupus-derived monoclonal autoantibodies against apoptotic chromatin recognize acetylated conformational epitopes.


OBJECTIVE:Nuclear components targeted by autoantibodies are a characteristic feature of the autoimmune disease systemic lupus erythematosus (SLE). The nucleosome, a major autoantigen, is released in patients with SLE as a result of a disturbed apoptosis and/or an insufficient clearance of apoptotic debris. During apoptosis the nucleosome is modified, thereby creating more immunogenic epitopes. Subsequently, epitope spreading will lead to the formation of autoantibodies against unmodified chromatin components. However, characterization of B cell epitopes specific for apoptotic chromatin modifications is hampered by the fact that the existing monoclonal antibodies (mAbs) were originally selected on non-apoptotic chromatin. Here, we describe a novel approach for generating mAbs from lupus mice that are specific for apoptosis-induced chromatin modifications. METHODS:Hybridomas were generated from pre-diseased and diseased lupus mice using standard fusion methods. Selection occurred on isolated apoptotic chromatin. Antibodies were further characterized by ELISA, western blot and immunofluorescence staining with apoptotic and non-apoptotic chromatin/cells. In addition, reactivity was determined with subnucleosomal complexes and with nucleosomes treated with trypsin or DNase I. Finally, reactivity was determined with cells treated with the histone deacetylase inhibitor TSA. RESULTS:Most generated mAbs appeared to be nucleosome specific with a clear preference for apoptotic nucleosomes compared to normal nucleosomes. Although the exact elucidation of the epitopes of these mAbs specific for apoptosis-associated nucleosome modifications remains a major challenge, the epitopes contain both DNA and histones, whereby the histone tails play a role in establishing the epitopes. Most importantly, the conformational epitopes of these nucleosome-specific antibodies seem to contain acetylated residues. CONCLUSIONS:Our approach, yielding a new panel of anti-apoptotic-chromatin antibodies, should facilitate the discovery of more apoptosis-induced chromatin modifications and their identification as key autoantigens in the pathogenesis of SLE.


Mol Immunol


Molecular immunology


van Bavel CC,Dieker JW,Tamboer WP,van der Vlag J,Berden JH




Has Abstract


2010-11-01 00:00:00














  • Reaction with, and fine structural recognition of polyamines by human IgE antibodies.

    abstract::Human IgE antibodies from nine allergic subjects were found to react with poly-L-lysine (PLL) and other polyamines. Radioimmunoassay inhibition studies indicated that the two amino groups, but not the carboxyl, in lysine contributed to the antibody binding and 4-aminomethyl-1,8-octanediamine, a compound containing thr...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Zhao Z,Baldo BA,O'Brien RM,Plomley RF

    更新日期:2000-04-01 00:00:00

  • Translocations into human chromosome 14 JH region: factors influencing downstream abortive immunoglobulin class switching.

    abstract::Bcl-2 translocations in follicular lymphomas (FL) are often associated with downstream immunoglobulin class switch recombination (CSR) on the translocated allele. We studied cell lines with different translocations into the IgH locus to gauge any common features associated with downstream CSR events. CSR associated wi...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Hughes JA,Weckert HA,van Holst Pellekaan C,Benson EM,Dunn IS

    更新日期:2003-12-01 00:00:00

  • A single backmutation in the human kIV framework of a previously unsuccessfully humanized antibody restores the binding activity and increases the secretion in cos cells.

    abstract::Humanization of rodent mAbs by CDR-grafting (also called "reshaping") is now a standard procedure for reducing immunogenicity and recruiting human effector functions. However, the design of the humanized mAb can sometimes prove circuitous. Attempts were made to humanize L-25, a mouse antibody against the human alpha-4...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Saldanha JW,Martin AC,Léger OJ

    更新日期:1999-08-01 00:00:00

  • Src-family kinases: rheostats of immune cell signaling.

    abstract::In immune cells, Src-family kinases have been implicated as critical regulators of a large number of intracellular signaling pathways. Studies of gene knockout mice lacking various family members have both confirmed the requirement for these kinases in some pathways and provided surprising insight into their roles in ...

    journal_title:Molecular immunology

    pub_type: 杂志文章,评审


    authors: Lowell CA

    更新日期:2004-07-01 00:00:00

  • B lymphocyte recognition of the self antigen mouse cytochrome C in different mouse strains: targeting of the same dominant epitope by naturally-occurring cells expressing distinct VH genes.

    abstract::Previously we reported that, early in the antibody response of BALB/c mice to several cytochromes c (CYT) coupled to ovalbumin (OVA), B cells responding to the self antigen mouse CYT recognized a single site on mouse CYT and were in much higher frequency than B cells responding to foreign CYT. In the present study the...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Mueller CM,Minnerath JM,Jemmerson R

    更新日期:1997-08-01 00:00:00

  • Signaling via the CytoR/JAK/STAT/SOCS pathway: Emergence during evolution.

    abstract::Cell-cell signaling represents an essential hallmark of multicellular organisms, which necessarily require a means of communicating between different cell populations, particularly immune cells. Cytokine receptor signaling through the Janus kinase/Signal Transducer and Activator of Transcription/Suppressor of Cytokine...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Liongue C,Taznin T,Ward AC

    更新日期:2016-03-01 00:00:00

  • Genes coding evolutionary novel anti-carbohydrate antibodies: studies on anti-Gal production in alpha 1,3galactosyltransferase knock out mice.

    abstract::This study analyzes the gene repertoire coding for antibodies to an evolutionary novel immunogenic carbohydrate antigen in mice. The alpha-gal epitope (Gal alpha 1-3Gal beta 1-4GlcNAc-R) is an autoantigen, abundantly expressed in wild type mice, but absent in alpha 1,3galactosyltransferase knock-out (KO) mice, where i...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Chen ZC,Radic MZ,Galili U

    更新日期:2000-06-01 00:00:00

  • Intracellular co-localization of SPLUNC1 protein with nanobacteria in nasopharyngeal carcinoma epithelia HNE1 cells depended on the bactericidal permeability increasing protein domain.

    abstract::Epithelial surfaces constitute natural immunobarriers against environmental threats. These barriers are brimming with fluids that bind, transport, cleave or degrade bacterial cells and their endotoxic by-products. Saliva and the airway surface-lining fluid (ASL) comprise the important fluid constituents. Short palate,...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Zhou HD,Li GY,Yang YX,Li XL,Sheng SR,Zhang WL,Zhao J

    更新日期:2006-04-01 00:00:00

  • The complement system is involved in acute inflammation but not in the hemorrhage produced by a Bothrops atrox snake venom low molecular mass proteinase.

    abstract::Low molecular weight hemorrhagins were purified from crude Bothrops atrox snake venom by gel filtration followed by ionic strength chromatography. The protein fractions obtained, designated HI-1 to HI-8, contained proteins with molecular masses lower than 30 kDa. HI-5, the most representative among of these fractions,...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Rodrigues FG,Petretski JH,Kanashiro MM,Lemos L,da Silva WD,Kipnis TL

    更新日期:2004-03-01 00:00:00

  • Dendritic cell development in infection.

    abstract::The immune system protects from infections primarily by detecting and eliminating invading pathogens. This is predominantly mediated by innate immune cells like neutrophils, monocytes and dendritic cells (DCs) expressing specific receptors recognizing pathogen-associated molecular patterns. DC activation by pathogens ...

    journal_title:Molecular immunology

    pub_type: 杂志文章,评审


    authors: Bieber K,Autenrieth SE

    更新日期:2020-05-01 00:00:00

  • Monitoring the formation of soluble immune complexes composed of idiotype and anti-idiotype antibodies by electron microscopy.

    abstract::We have previously used immunoelectron microscopy (IEM) to generate a three-dimensional map of idiotypic (Id) and isotypic epitopes on the Fab arms of HGAC 39 (Roux et al., 1987, Proc. natn. Acad. Sci. U.S.A. 84, 4984-4988), a mouse IgG3 monoclonal antibody (Mab). In this report, we analyse the geometry of the various...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Roux KH,Greenspan NS

    更新日期:1994-06-01 00:00:00

  • Amino acid sequence of the variable region of heavy chain in immunoglobulin (Mot) having unusual papain cleavage sites.

    abstract::An IgGl(lambda) Mot myeloma protein showed a unique susceptibility toward papain digestion. The Fab fragment of Mot was more digestible with papain than the Fc fragment. This phenomenon was found to occur by unusual cleavage of the Fd fragment with papain. Determination of the complete primary structure of the V regio...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Kojima M,Koide T,Odani S,Ono T

    更新日期:1986-02-01 00:00:00

  • A simple procedure for the isolation of human secretory IgA of IgA1 and IgA2 subclass by a jackfruit lectin, jacalin, affinity chromatography.

    abstract::Jackfruit lectin, jacalin, prepared from two batches of jackfruit seeds showed a different specificity in precipitating reaction in Agarose gel with various purified immunoglobulins and secretory components. Jacalin-P, extracted from jackfruit seeds from the Philippines, reacts only with serum IgA and secretory IgA of...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Kondoh H,Kobayashi K,Hagiwara K

    更新日期:1987-11-01 00:00:00

  • Molecular characterization of woodchuck CD4 (wCD4) and production of a depletion monoclonal antibody against wCD4.

    abstract::CD4 T cells play an important role in the immune response against hepatitis B virus (HBV) infection. Woodchucks represent an excellent animal model to study HBV infection. In this study, we characterized the cDNA sequence of woodchuck CD4 (wCD4). The deduced wCD4 protein has four extracellular immunoglobulin-like doma...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Yang Y,Zhang X,Zhang C,Tao Y,Fan W,Wang Z,Wang H,Lu M,Yang D,Fiedler M,Wang B

    更新日期:2013-11-01 00:00:00

  • Characterization of circulating and monocyte-derived dendritic cells in obese and diabetic patients.

    abstract::Dendritic cells (DCs) are suspected to be involved in the development of atherogenesis, but their role is still unclear. The aim of this study was to characterize circulating DCs and monocyte-derived DCs (Mo-DCs) of obese and diabetic patients (T2D), and to study their interaction with human coronary smooth muscle cel...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Musilli C,Paccosi S,Pala L,Gerlini G,Ledda F,Mugelli A,Rotella CM,Parenti A

    更新日期:2011-10-01 00:00:00

  • Comparative analysis of human and mouse 3' Igh regulatory regions identifies distinctive structural features.

    abstract::Immunoglobulin heavy chain (Igh) locus rearrangements are controlled in part by an approximately 30 b complex 3' regulatory region located 3' of C alpha: this region contains several enhancers. We report here the comparison of the genomic sequences of the 3' regulatory region and further downstream sequences from mous...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Sepulveda MA,Garrett FE,Price-Whelan A,Birshtein BK

    更新日期:2005-03-01 00:00:00

  • Dynamic DNA methylation patterns across the mouse and human IL10 genes during CD4+ T cell activation; influence of IL-27.

    abstract::IL-10 plays a critical role in controlling inflammation and the anti-inflammatory functions of IL-10 are regulated based on its coordinated expression from various cellular sources, most notably T cells. Although nearly all CD4+ subpopulations can express IL-10, surprisingly little is known about the molecular mechani...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Hedrich CM,Ramakrishnan A,Dabitao D,Wang F,Ranatunga D,Bream JH

    更新日期:2010-11-01 00:00:00

  • The Cbl-b RING finger domain has a limited role in regulating inflammatory cytokine production by IgE-activated mast cells.

    abstract::The RING finger type E3 ubiquitin ligase, Cbl-b, is abundantly expressed in bone marrow-derived mast cells (BMMCs) and functions as a potent negative regulator of signalling responses from the high-affinity IgE receptor (FcvarepsilonRI). To determine the contribution of Cbl-b E3 ligase activity we generated knockin mi...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Oksvold MP,Dagger SA,Thien CB,Langdon WY

    更新日期:2008-02-01 00:00:00

  • p38 mitogen-activated protein kinases (MAPKs) are involved in intestinal immune response to bacterial muramyl dipeptide challenge in Ctenopharyngodon idella.

    abstract::The p38 mitogen-activated protein kinases (MAPKs) are essential cytoplasmic signal molecules of innate immune pathways that play a vital role in host immune defense responses to pathogenic challenges. In this study, two fish p38 genes (Cip38α and Cip38β) were characterized for the first time from the grass carp Ctenop...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Sun Y,Xu W,Li D,Zhou H,Qu F,Cao S,Tang J,Zhou Y,He Z,Li H,Zhou Z,Liu Z

    更新日期:2020-02-01 00:00:00

  • Dmu expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2-/- mice even if combined with Bcl-2.

    abstract::Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dmu protein. Dmu can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length mu, but cannot promote the pro-B to pre-B cell transition of Rag-/- B cells. In order to dete...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Wikström I,Bergqvist I,Holmberg D,Forssell J

    更新日期:2006-03-01 00:00:00

  • Cloning, expression and characterization of mugwort pollen allergen Art v 2, a pathogenesis-related protein from family group 1.

    abstract::Mugwort (Artemisia vulgaris) belongs to the Compositae family, and is one of the main causes of allergy in late summer and autumn. The aim of the study was to characterize the allergen Art v 2 from mugwort pollen. Skin prick tests, performed in 19 patients allergic to mugwort and 10 control patients, showed an Art v 2...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Arilla MC,Ibarrola I,Puente Y,Daza JC,Martínez A,Asturias JA

    更新日期:2007-07-01 00:00:00

  • MicroRNA-146a promotes IgE class switch in B cells via upregulating 14-3-3σ expression.

    abstract::B cells play a critical role in immune responses both in physiological and pathological conditions, and microRNAs have been shown to play important roles in regulating B cell proliferation and function. MiR-146a has been shown to modulate T cell immunity, but its function in regulating B cell response remains partiall...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Li F,Huang Y,Huang YY,Kuang YS,Wei YJ,Xiang L,Zhang XJ,Jia ZC,Jiang S,Li JY,Wan Y

    更新日期:2017-12-01 00:00:00

  • Divergent roles of histone deacetylase 6 (HDAC6) and histone deacetylase 11 (HDAC11) on the transcriptional regulation of IL10 in antigen presenting cells.

    abstract::The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune responses. Histone deacetylases (HDACs) have been widely described as n...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Cheng F,Lienlaf M,Perez-Villarroel P,Wang HW,Lee C,Woan K,Woods D,Knox T,Bergman J,Pinilla-Ibarz J,Kozikowski A,Seto E,Sotomayor EM,Villagra A

    更新日期:2014-07-01 00:00:00

  • A marker of human foetal endoderm defined by a monoclonal antibody involves Type 1 blood group chains.

    abstract::This report demonstrates that a marker of human embryonic endoderm and embryonal carcinoma cells recognized by a hybridoma antibody FC 10.2, involves Type 1 blood group chains with the sequence Gal beta 1 leads to 3G1cNAc beta 1 leads to 3Gal beta 1 leads to 4G1c. This conclusion has been reached from antigenic analys...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Gooi HC,Williams LK,Uemura K,Hounsell EF,McIlhinney RA,Feizi T

    更新日期:1983-06-01 00:00:00

  • Antigens of activated rat T lymphocytes including a molecule of 50,000 Mr detected only on CD4 positive T blasts.

    abstract::Mouse monoclonal antibodies (MAbs) have been prepared against rat T cell blasts. One MAb called MRC OX-40 recognized an antigen that differed from any previously described in that its expression was detected only on T blasts that also expressed the CD4 antigen. The OX-40 MAb did not detect an activation determinant of...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Paterson DJ,Jefferies WA,Green JR,Brandon MR,Corthesy P,Puklavec M,Williams AF

    更新日期:1987-12-01 00:00:00

  • MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA.

    abstract::Sepsis is a life-threatening disease characterized by uncontrolled inflammatory responses upon pathogen infections, especially for the antibiotic-resistant strains, such as Methicillin-resistant S. aureus (MRSA). Here we demonstrated that a Mitochondria-derived peptide (MOTS-c) could significantly improve the survival...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Zhai D,Ye Z,Jiang Y,Xu C,Ruan B,Yang Y,Lei X,Xiang A,Lu H,Zhu Z,Yan Z,Wei D,Li Q,Wang L,Lu Z

    更新日期:2017-12-01 00:00:00

  • The Fli-1 transcription factor is a critical regulator for controlling the expression of chemokine C-X-C motif ligand 2 (CXCL2).

    abstract::Mammalian cells produce inflammatory cytokines and chemokines in response to innate immune signals and their expression is tightly regulated. Chemokine (C-X-C motif) ligand 2 (CXCL2), also known as macrophage inflammatory protein 2-alpha (MIP2-alpha), is an inflammatory chemokine belonging to the CXC chemokine family....

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Lou N,Lennard Richard ML,Yu J,Kindy M,Zhang XK

    更新日期:2017-01-01 00:00:00

  • Maspin inhibits macrophage phagocytosis and enhances inflammatory cytokine production via activation of NF-κB signaling.

    abstract::Maspin (mammary serine protease inhibitor) is a non-inhibitory member of the serine protease inhibitor superfamily and a tumor suppressor in several cancers due to its ability to inhibit cell invasion, angiogenesis, and promote apoptosis. However, its immunomodulatory function remains largely unexplored. Thus, we expl...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Wang Y,Sun L,Song Z,Wang D,Bao Y,Li Y

    更新日期:2017-02-01 00:00:00

  • DNA immunization via intramuscular and intradermal routes using a gene gun provides different magnitudes and durations on immune response.

    abstract::We investigated the antibody (Ab) and cytotoxic T lymphocyte (CTL) responses to gene gun (GG)-mediated DNA immunization via the intramuscular (i.m.) and intradermal (i.d.) routes. BALB/c mice were immunized five times at weekly intervals with plasmid DNA encoding enhanced green fluorescent protein (EGFP). EGFP product...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Ito K,Ito K,Shinohara N,Kato S

    更新日期:2003-05-01 00:00:00

  • Molecular basis of allergen cross-reactivity: non-specific lipid transfer proteins from wheat flour and peach fruit as models.

    abstract::Peach non-specific lipid transfer protein (Pru p 3; nsLTP) has been characterized as the major food allergen in the adult Mediterranean population. Its wheat homologous protein, Tri a 14 has a relevant inhalant allergen in occupational baker's asthma. Different sensitization patterns to these allergens have been found...

    journal_title:Molecular immunology

    pub_type: 杂志文章


    authors: Tordesillas L,Pacios LF,Palacin A,Quirce S,Armentia A,Barber D,Salcedo G,Diaz-Perales A

    更新日期:2009-12-01 00:00:00