Naturally occurring B-cell autoreactivity: A critical overview

Avraméas, Stratis; Ternynck, Thérèse; Tsonis, Ioannis; Lymberi, Peggy

doi:10.1016/j.jaut.2007.07.010

Cited by 101 publications

(78 citation statements)

References 67 publications

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“…Natural antibodies are produced in the absence of external antigenic stimulation and are directed against a wide spectrum of self-and non-self antigens (Avrameas et al, 2007); their role is related to early protection against pathogens (Ochsenbein et al, 1999;Baumgarth et al, 2005;McCoy et al, 2006). On the other hand, high levels of IgEs in conjunction with increased levels of eosinophils are often seen in the circulation of allergic individuals and are thought to arise because T cells orient towards the Th2 phenotype (Yazdanbakhsh et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Gain of function of the immune system caused by a ryanodine receptor 1 mutation

Vukcevic

Zorzato

Keck

et al. 2013

Journal of Cell Science

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SummaryMutations in RYR1, the gene encoding ryanodine receptor 1, are linked to a variety of neuromuscular disorders including malignant hyperthermia (MH), a pharmacogenetic hypermetabolic disease caused by dysregulation of Ca 2+ in skeletal muscle. RYR1 encodes a Ca 2+ channel that is predominantly expressed in skeletal muscle sarcoplasmic reticulum, where it is involved in releasing the Ca 2+ necessary for muscle contraction. Other tissues, however, including cells of the immune system, have been shown to express ryanodine receptor 1; in dendritic cells its activation leads to increased surface expression of major histocompatibility complex II molecules and provides synergistic signals leading to cell maturation. In the present study, we investigated the impact of an MH mutation on the immune system by studying the RYR1 Y522S knock-in mouse. Our results show that there are subtle but significant differences both in resting 'non-challenged' mice as well as in mice treated with antigenic stimuli, in particular the knock-in mice: (i) have dendritic cells that are more efficient at stimulating T cell proliferation, (ii) have higher levels of natural IgG 1 and IgE antibodies, and (iii) are faster and more efficient at mounting a specific immune response in the early phases of immunization. We suggest that some gain-of-function MH-linked RYR1 mutations might offer selective immune advantages to their carriers. Furthermore, our results raise the intriguing possibility that pharmacological activation of RyR1 might be exploited for the development of new classes of vaccines and adjuvants.

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Section: Discussionmentioning

confidence: 99%

Gain of function of the immune system caused by a ryanodine receptor 1 mutation

Vukcevic

Zorzato

Keck

et al. 2013

Journal of Cell Science

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“…NAbs exist in the serum and other body fluids (35)(36)(37)(38) even before the entrance of antigen and they exert various roles, such as the first line of defense against bacterial and viral infections, the clearance of cell debris after apoptosis, as well as the regulation of immune and other physiological systems (4,37). Although they can consist of various Ab isotypes, the vast majority of NAbs are represented by IgM (4).…”

Section: Discussionmentioning

confidence: 99%

“…Although they can consist of various Ab isotypes, the vast majority of NAbs are represented by IgM (4). IgM is the first Ab produced in an ongoing immune response to infection and/or immunization, and it is always The existence of hexameric IgM was confirmed decades ago (39), but the experimental data concerning its biological function(s) still lack.…”

Section: Discussionmentioning

confidence: 99%

“…B lymphocytes (4) called B-1a cells (8) and express various biological functions-they contribute to the defense and elimination of bacteria and viruses, participate in the removal of apoptotic cells, as well as in the regulation of B and T cells, cytokine action and inflammation, to name some (4). NAbs are mostly represented by immunoglobulin (Ig) M although other Ab isotypes, such as IgG and IgA can be found too (4).…”

Section: Introductionmentioning

confidence: 99%

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Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers

et al. 2011

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Natural antibodies (NAbs) are present in circulation even before the exposure to antigen and they exert various biological functions. They are polyreactive and mainly represented by immunoglobulin M (IgM), which is the first antibody produced in an ongoing immune response to infection and/or immunization. IgM is always secreted as a polymer with predominant pentameric structure, although other polymeric forms such as hexamer can be also formed. The biological functions of hexameric IgM are still not known and it is proposed that its existence as a NAb could be deleterious. However, the nature of IgM hexamers has not been investigated yet. In this paper, we have tested the expression of natural idiotope and antigenic specificities of pentameric and hexameric IgM polymers originating from sera of patients with Waldenström's macroglobulinemia, as well as patients suffering from recurrent urinary bacterial infections. We demonstrate that although pentameric IgM polymers can exist as natural and immune antibodies, IgM hexamers are exclusively immune and do not exist as NAbs.

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“…A utoantibodies are often associated with autoimmune pathogenesis, as indicated by correlations with various symptomatic manifestations, laboratory findings, deposition of immune complexes in pathological specimens, and recapitulation of diseases by serum transfer (1)(2)(3)(4). Peritoneal B cells are thought to be the source of autoantibody-producing long-lived plasma cells in various autoimmune-prone mice such as New Zealand Black (NZB) and BXSB mice (5,6), and mice genetically engineered for various molecules involved in signal transduction pathways of B cell survival and apoptosis (7)(8)(9)(10)(11)(12)(13)(14) …”

mentioning

confidence: 99%

JNK Regulatory Molecule G5PR Induces IgG Autoantibody–Producing Plasmablasts from Peritoneal B1a Cells

Kitabatake

Soma

Zhang

et al. 2015

The Journal of Immunology

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Peritoneal B1a cells expressing CD5 and CD11b generate autoantibody-producing precursors in autoimmune-prone mice. Previous studies show reduced JNK signaling in peritoneal B1a cells of female New Zealand Black mice and an abnormal increase of protein phosphatase 2A subunit G5PR that regulates BCR-mediated JNK signaling as a cause of autoimmunity. To investigate the mechanism regulating B1a differentiation into autoantibody-secreting plasmablasts (PBs), we applied an in vitro culture system that supports long-term growth of germinal center (GC) B cells (iGB) with IL-4, CD40L, and BAFF. Compared with spleen B2 cells, B1a cells differentiated into GC-like B cells, but more markedly into PBs, and underwent class switching toward IgG1. During iGB culture, B1a cells expressed GC-associated aicda, g5pr, and bcl6, and markedly PB-associated prdm1, irf4, and xbp1. B1a-derived iGB cells from New Zealand Black × New Zealand White F1 mice highly differentiated into autoantibody-secreting PBs in vitro and localized to the GC area in vivo. In iGB culture, JNK inhibitor SP600125 augmented the differentiation of C57BL/6 B1a cells into PBs. Furthermore, B1a cells from G5PR transgenic mice markedly differentiated into IgM and IgG autoantibody–secreting PBs. In conclusion, JNK regulation is critical to suppress autoantibody-secreting PBs from peritoneal B1a cells.

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Naturally occurring B-cell autoreactivity: A critical overview

Cited by 101 publications

References 67 publications

Gain of function of the immune system caused by a ryanodine receptor 1 mutation

Gain of function of the immune system caused by a ryanodine receptor 1 mutation

Antigenic specificity and expression of a natural idiotope on human pentameric and hexameric IgM polymers

JNK Regulatory Molecule G5PR Induces IgG Autoantibody–Producing Plasmablasts from Peritoneal B1a Cells

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