Peroxisome Proliferator-Activated Receptor γ B Cell-Specific-Deficient Mice Have an Impaired Antibody Response.
ABSTRACT Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily. PPARγ, a ligand-activated transcription factor, has important anti-inflammatory and antiproliferative functions, and it has been associated with diseases including diabetes, scarring, and atherosclerosis, among others. PPARγ is expressed in most bone marrow-derived cells and influences their function. PPARγ ligands can stimulate human B cell differentiation and promote Ab production. A knowledge gap is that the role of PPARγ in B cells under physiological conditions is not known. We developed a new B cell-specific PPARγ (B-PPARγ) knockout mouse and explored the role of PPARγ during both the primary and secondary immune response. In this article, we show that PPARγ deficiency in B cells decreases germinal center B cells and plasma cell development, as well as the levels of circulating Ag-specific Abs during a primary challenge. Inability to generate germinal center B cells and plasma cells is correlated to decreased MHC class II expression and decreased Bcl-6 and Blimp-1 levels. Furthermore, B-PPARγ-deficient mice have an impaired memory response, characterized by low titers of Ag-specific Abs and low numbers of Ag-experienced, Ab-secreting cells. However, B-PPARγ-deficient mice have no differences in B cell population distribution within primary or secondary lymphoid organs during development. This is the first report, to our knowledge, to show that, under physiological conditions, PPARγ expression in B cells is required for an efficient B cell-mediated immune response as it regulates B cell differentiation and Ab production.
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ABSTRACT: Influenza viruses remain a critical global health concern. More efficacious vaccines are needed to protect against influenza virus, yet few adjuvants are approved for routine use. Specialized proresolving mediators (SPMs) are powerful endogenous bioactive regulators of inflammation, with great clinical translational properties. In this study, we investigated the ability of the SPM 17-HDHA to enhance the adaptive immune response using an OVA immunization model and a preclinical influenza vaccination mouse model. Our findings revealed that mice immunized with OVA plus 17-HDHA or with H1N1-derived HA protein plus 17-HDHA increased Ag-specific Ab titers. 17-HDHA increased the number of Ab-secreting cells in vitro and the number of HA-specific Ab-secreting cells present in the bone marrow. Importantly, the 17-HDHA-mediated increased Ab production was more protective against live pH1N1 influenza infection in mice. To our knowledge, this is the first report on the biological effects of ω-3-derived SPMs on the humoral immune response. These findings illustrate a previously unknown biological link between proresolution signals and the adaptive immune system. Furthermore, this work has important implications for the understanding of B cell biology, as well as the development of new potential vaccine adjuvants.The Journal of Immunology 11/2014; 193(12). DOI:10.4049/jimmunol.1302795 · 5.36 Impact Factor
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ABSTRACT: Adopted orphan nuclear receptors, such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors (LXRs), have emerged as key regulators of inflammation and immunity and likewise control skeletal homeostasis. These properties render them attractive targets for the therapy of various inflammatory and autoimmune diseases affecting the musculoskeletal system. This review summarises the current knowledge on the role of these families of receptors during innate and adaptive immunity as well as during the control of bone turnover and discuss the potential use of targeting these molecules during the treatment of chronic diseases such as osteoarthritis, rheumatoid arthritis and osteoporosis.Swiss medical weekly: official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology 12/2014; 144:w14055. DOI:10.4414/smw.2014.14055 · 1.88 Impact Factor