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Protective Roles of Natural IgM Antibodies.

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TLDR
Recent progress is reviewed in the understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.
Abstract
Antibodies are a vital part of the armamentarium of the adaptive immune system for the fine-tuning of the recognition and response to foreign threats. However, in health there are some types of antibodies that instead recognize self-antigens and these contribute to the enhancement of primitive innate functions. This repertoire of natural IgM antibodies is postulated to have been selected during immune evolution for their contributions to critical immunoregulatory and housekeeping properties. The clearance of dying cells is one of the most essential responsibilities of the immune system, which is required to prevent uncontrolled inflammation and autoimmunity. In the murine immune system, natural IgM antibodies that recognize apoptotic cells have been shown to enhance the phagocytic clearance of dead and dying cells and to suppress innate immune signaling pathways. In the mouse, natural IgM are often the products of B-1 cell clones that arise during immune development without an absolute requirement for exogenous antigenic stimulation. In patients with systemic lupus erythematosus, IgM autoantibodies, which bind to neo-epitopes on apoptotic cells, have been demonstrated to be present at significantly higher levels in patients with lower disease activity and with less severe organ damage. While certain specificities of IgM autoantibodies correlate with protection from lupus renal disease, others may convey protective properties from lupus-associated atherosclerotic cardiovascular disease. New and unexpected insights into the functional roles of IgM antibodies are still emerging, especially regarding the functions of natural antibodies. Herein, we review recent progress in our understanding of the potential roles of natural IgM autoantibodies in the regulation of immune homeostasis and for protection from autoimmune and inflammatory diseases.

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Immunity, atherosclerosis and cardiovascular disease

TL;DR: To prove that inflammation is a cause of atherosclerosis and CVD, clinical studies with anti-inflammatory and/or immune-modulatory treatment are needed and how inflammation can be targeted therapeutically to provide novel treatments for CVD are reviewed.
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B Cells, Antibodies, and More

TL;DR: The multifaceted roles of B cells as enhancers and regulators of immunity with relevance to kidney disease and transplantation are discussed.
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B Cells in Autoimmune Diseases

TL;DR: The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers.
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Targeting B Cells and Plasma Cells in Autoimmune Diseases

TL;DR: The findings suggest that B lineage cells not only produce pathogenic autoantibodies, but also significantly contribute to the regulation of inflammation, in the context of recent findings using B lineage targeting therapies.
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Defining Natural Antibodies

TL;DR: The current knowledge of NAbs is summarized in the context of initiating a discussion within the field of how such an important and multifaceted group of molecules should be defined.
References
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Journal ArticleDOI

Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

TL;DR: It is reported that Hmgb1-/- necrotic cells have a greatly reduced ability to promote inflammation, which proves that the release of HMGB1 can signal the demise of a cell to its neighbours, and cells undergoing apoptosis are programmed to withhold the signal that is broadcast by cells that have been damaged or killed by trauma.
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RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

TL;DR: It is reported here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily.
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Molecular identification of a danger signal that alerts the immune system to dying cells

TL;DR: Uric acid stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from CD8+ T cells, and have important implications for vaccines, autoimmunity and inflammation.
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How dying cells alert the immune system to danger

TL;DR: Current knowledge of cell death and repair processes in the host and their importance to host defence and disease pathogenesis has only been appreciated relatively recently is reviewed.
Journal ArticleDOI

Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-κB pathway

TL;DR: It is reported here that heat shock proteins (HSP), the most abundant and conserved mammalian molecules, constitute such an internal signal that provides a unified mechanism for response to internal and external stimuli.
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