An immune response needs to be tightly regulated to prevent excessive inflammation, which may result in the destruction of healthy tissues. At the molecular level, the strength of an immune response is determined by the integration of a multitude of positive and negative signals. This review will focus on IgG-dependent immune responses and discuss how the inhibitory receptor FcγRIIB may be involved in regulating both the afferent and efferent phases of such a response. Furthermore, we will discuss recent evidence suggesting that FcγRIIB may have important functions beyond the negative regulation of signals transduced by the B-cell receptor or activating FcγRs and could be responsible for the activity of agonistic antibodies in vivo.
"In a similar manner nonfunctional Fcí µí»¾RIIB alleles or promoter polymorphisms causing a lower expression level have been associated with the development or severity of human and mouse autoimmune diseases and humanized mice transplanted with a human immune system carrying the nonfunctional Fcí µí»¾RIIB allele in a homozygous fashion start to develop autoantibodies [13, 26–30]. As this interesting gatekeeper function of Fcí µí»¾RIIB is not the main focus of this paper, the interested reader is directed to several excellent recent reviews covering this in greater detail    "
[Show abstract][Hide abstract] ABSTRACT: In retrospect, the therapeutic potential of immunoglobulins was first demonstrated by von Behring and Kitasato in the late nineteenth century by protecting mice from the lethal effects caused by tetanus and diphtheria toxin via injection of a hyperimmune serum generated in rabbits. Even today, hyperimmune sera generated from human donors with high serum titers against a certain pathogen are still in use as a means of providing passive protection. More importantly, therapeutic antibodies specific for malignant or autoreactive cells have become included in the standard of care in diseases such as breast cancer and malignant lymphoma. Despite this clinical success, we are only at the beginning of understanding the precise molecular and cellular pathways responsible for immunoglobulin G (IgG) activity in vivo. Since then, an enormous amount of information about the mechanism of IgG activity has been obtained in various model systems. The aim of this review is to provide a comprehensive overview of our current understanding of how IgG antibodies mediate their activity in vivo and how we can use this knowledge to enhance the activity of therapeutic antibodies or block the proinflammatory and tissue pathology inducing activity of autoantibodies.
[Show abstract][Hide abstract] ABSTRACT: Intravenous immunoglobulin (IVIG) preparations comprise pooled IgG antibodies from the serum of thousands of donors and were initially used as an IgG replacement therapy in immunocompromised patients. Since the discovery, more than 30 years ago, that IVIG therapy can ameliorate immune thrombocytopenia, the use of IVIG preparations has been extended to a wide range of autoimmune and inflammatory diseases. Despite the broad efficacy of IVIG therapy, its modes of action remain unclear. In this Review, we cover the recent insights into the molecular and cellular pathways that are involved in IVIG-mediated immunosuppression, with a particular focus on IVIG as a therapy for IgG-dependent autoimmune diseases.
[Show abstract][Hide abstract] ABSTRACT: Seventh European Workshop on Immune-Mediated Inflammatory Diseases 2012 Noordwijk aan Zee, The Netherlands, 28-30 November 2012 The European Workshop on Immune-Mediated Inflammatory Diseases aims to exchange scientific knowledge and promote the collaboration between various disciplines (rheumatology, dermatology and gastroenterology) among physicians and scientists. This year ophthalmologists and neurologists were also present for the first time. The meeting revolved around the following topics: fibrosis, gene therapy in ophthalmology, functional genomics, challenges in human immunology, environmental factors, diabetes and metabolism, novelties in multiple sclerosis and innate lymphoid cells. The workshop was preceded by a masterclass that covered the last 15 years of IL-17/Th17 research and provided an overview on future therapeutics to battle immune-mediated inflammatory diseases.
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