Ontology highlight
ABSTRACT:
PROVIDER: PRJNA988832 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25056561_1.fastq.gz | Fastqsanger.gz | |||
| SRR25056561_2.fastq.gz | Fastqsanger.gz | |||
| SRR25056562_1.fastq.gz | Fastqsanger.gz | |||
| SRR25056562_2.fastq.gz | Fastqsanger.gz | |||
| SRR25056563_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement
2009-02-19 | GSE14862 | GEO
Project description:Intestinal ischemia-reperfusion (IR) injury is initiated when natural IgM antibodies recognize neo-epitopes that are revealed on ischemic cells. The target molecules and mechanisms whereby these neo-epitopes become accessible to recognition are not well understood. Proposing that isolated intestinal epithelial cells (IEC) may carry IR-related neo-epitopes, we used in vitro IEC binding assays to screen hybridomas created from B cells of unmanipulated wild type C57BL/6 mice. We identified a novel IgM monoclonal antibody (mAb B4) that reacted with the surface of IEC by flow cytometric analysis and was alone capable of causing complement activation, neutrophil recruitment and intestinal injury in otherwise IR-resistant Rag1-/- mice. Monoclonal Ab B4 was found to specifically recognize mouse annexin IV. Pre-injection of recombinant annexin IV blocked IR injury in wild type C57BL/6 mice, demonstrating the requirement for recognition of this protein in order to develop IR injury in the context of a complex natural antibody repertoire. Humans were also found to exhibit IgM natural antibodies that recognize annexin IV. These data in toto identify annexin IV as a key ischemia-related target antigen that is recognized by natural Abs in a pathologic process required in vivo to develop intestinal IR injury. Keywords: Natural antibodies, Annexin, Ischemia Reperfusion, Inflammation, Complement In the study presented here, a total of 4 custom spotted antigen slides were hybridized with known antibodies.
2010-05-05 | E-GEOD-14862 | biostudies-arrayexpress
Project description:Natural antibodies, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neo-antigenic determinants on apoptotic thymocytes is dominated by antibodies to oxidation-associated antigens, phosphorylcholine (PC), a head group that becomes exposed during programmed-cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive-oxidation species. While natural antibodies to apoptotic cells in naM-CM-/ve adult mice were dominated by PC and MDA specificities, the amounts of these antibodies were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA antibodies was affected by VH gene inheritance. Antibody interactions with apoptotic-cells also mediated the recruitment of C1q, which alone can promote apoptotic-cell phagocytosis by immature dendritic cells. Significantly, IgM-antibodies to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic-cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural antibodies that recognize neo-antigens on apoptotic cells, in naM-CM-/ve mice and those induced by immune exposure to apoptotic-cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells. Keywords: Natural antibodies, Inflammation, Complement, Apoptosis In the study presented here, a total of 11 custom-spotted protein slides were hybridized with a T15 IgM monoclonal antibody at three different concentrations, an isotype control IgM, 2 slides were hybridized with serum from naM-QM-^Wve mice, 2 slides incubated with serum from mice immunized with apoptotic cells, 2 slides were incubated with serum from mice immunized with saline, and a negative control slide with no antibody hybridized
2009-02-23 | E-GEOD-14958 | biostudies-arrayexpress
Project description:Immunoglobulin mu (IgM) is a class of mammalian antibodies that are critical for the early stages of adaptive immunity and are the most potent activators of the classical complement cascade. While the relationship between IgM and complement has been appreciated for decades, the structural transitions within IgM upon antigen binding that lead to the activation of the C1 complex remain unresolved. Here we examine the complement activation profiles, binding kinetics, and conformational changes in IgM in different antigen-bound states. Only in the complex with a surface-displayed antigen with multiple Fab arms engaged was the IgM fully capable of driving complement activation. The structural changes within IgM upon antigen binding were monitored by Hydrogen/Deuterium Exchange reveal the predominant structural changes within the Fc core domains upon activation. Collectively, this work establishes key structural and functional qualities that define the complement-active form of IgM.
2025-04-02 | PXD056918 | Pride
Project description:Immunoglobulin mu (IgM) is a class of mammalian antibodies that are critical for the early stages of adaptive immunity and are the most potent activators of the classical complement cascade. While the relationship between IgM and complement has been appreciated for decades, the structural transitions within IgM upon antigen binding that lead to the activation of the C1 complex remain unresolved. Here we examine the complement activation profiles, binding kinetics, and conformational changes in IgM in different antigen-bound states. Only in the complex with a surface-displayed antigen with multiple Fab arms engaged was the IgM fully capable of driving complement activation. The structural changes within IgM upon antigen binding were monitored by Hydrogen/Deuterium Exchange reveal the predominant structural changes within the Fc core domains upon activation. Collectively, this work establishes key structural and functional qualities that define the complement-active form of IgM.
2025-04-02 | PXD056670 | Pride
Project description:Immunoglobulin mu (IgM) is a class of mammalian antibodies that are critical for the early stages of adaptive immunity and are the most potent activators of the classical complement cascade. While the relationship between IgM and complement has been appreciated for decades, the structural transitions within IgM upon antigen binding that lead to the activation of the C1 complex remain unresolved. Here we examine the complement activation profiles, binding kinetics, and conformational changes in IgM in different antigen-bound states. Only in the complex with a surface-displayed antigen with multiple Fab arms engaged was the IgM fully capable of driving complement activation. The structural changes within IgM upon antigen binding were monitored by Hydrogen/Deuterium Exchange reveal the predominant structural changes within the Fc core domains upon activation. Collectively, this work establishes key structural and functional qualities that define the complement-active form of IgM.
2025-04-02 | PXD056897 | Pride
Project description:Immunoglobulin mu (IgM) is a class of mammalian antibodies that are critical for the early stages of adaptive immunity and are the most potent activators of the classical complement cascade. While the relationship between IgM and complement has been appreciated for decades, the structural transitions within IgM upon antigen binding that lead to the activation of the C1 complex remain unresolved. Here we examine the complement activation profiles, binding kinetics, and conformational changes in IgM in different antigen-bound states. Only in the complex with a surface-displayed antigen with multiple Fab arms engaged was the IgM fully capable of driving complement activation. The structural changes within IgM upon antigen binding were monitored by Hydrogen/Deuterium Exchange reveal the predominant structural changes within the Fc core domains upon activation. Collectively, this work establishes key structural and functional qualities that define the complement-active form of IgM.
2025-10-14 | PXD056697 | Pride
Project description:Human serum IgM antibodies are composed of heavily glycosylated polymers with five glycosylation sites on the μ (heavy) chain and one glycosylation site on the J chain. In contrast to IgG glycans, which are vital for a number of biological functions, virtually nothing is known about structure-function relationships of IgM glycans. Natural IgM is the earliest immunoglobulin produced and recognizes multiple antigens with low affinity, whilst immune IgM is induced by antigen exposure and is characterized by a higher antigen specificity. Natural anti-lymphocyte IgM is present in the serum of healthy individuals and increases in inflammatory conditions. It is able to inhibit T cell activation, but the underlying molecular mechanism is not understood. Here we show, for the first time, that sialylated N-linked glycans induce the internalization of IgM by T cells, which in turn causes severe inhibition of T cell responses. The absence of sialic acid residues abolishes these inhibitory activities, showing a key role of sialylated N-glycans in inducing the IgM-mediated immune suppression.
2014-11-11 | E-MTAB-3030 | biostudies-arrayexpress
Project description:Endogenous retroviruses (ERV), comprising a substantial portion of the vertebrate genome, are remnants of ancient genetic invaders. ERV with near-intact coding potential reactivate in B cell-deficient mice. Here, we employed an antigen-baiting strategy to enrich B cells reactive to ERV surface antigens. We identified ERV-reactive B-1 cells expressing germline-encoded natural IgM antibodies in naïve mice, the level of which further increases upon innate immune sensor stimulation. B cell receptor repertoire profiling of ERV-reactive B-1 cells revealed increased usage of Igh VH gene that gives rise to glycan-specific antibodies targeting terminal N-acetylglucosamine moieties on ERV glycoproteins, which further engage the complement pathway to protect the host from ERV emergence. These same antibodies also recognize glycoproteins of other enveloped viruses, but not self-proteins. These results reveal an innate antiviral mechanism of germline-encoded antibodies with broad reactivity to enveloped viruses, whose absence leads to the emergence of infectious ERV.
2023-07-01 | GSE207247 | GEO
Project description:Natural antibodies, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neo-antigenic determinants on apoptotic thymocytes is dominated by antibodies to oxidation-associated antigens, phosphorylcholine (PC), a head group that becomes exposed during programmed-cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive-oxidation species. While natural antibodies to apoptotic cells in naïve adult mice were dominated by PC and MDA specificities, the amounts of these antibodies were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA antibodies was affected by VH gene inheritance. Antibody interactions with apoptotic-cells also mediated the recruitment of C1q, which alone can promote apoptotic-cell phagocytosis by immature dendritic cells. Significantly, IgM-antibodies to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic-cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural antibodies that recognize neo-antigens on apoptotic cells, in naïve mice and those induced by immune exposure to apoptotic-cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells. Keywords: Natural antibodies, Inflammation, Complement, Apoptosis
2009-02-23 | GSE14958 | GEO