Peroxisome Proliferator-Activated Receptor γ B Cell-Specific–Deficient Mice Have an Impaired Antibody Response
| Autor: | Thomas I. Murant, Richard P. Phipps, Safiehkhatoon Moshkani, Andrea Bottaro, Simona Bancos, Sesquile Ramon, Julie Sahler, Patricia J. Sime, Thomas H. Thatcher |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Cellular differentiation Plasma Cells Immunology Peroxisome proliferator-activated receptor Biology DNA-binding protein Antibodies Article Mice Antibody Specificity Internal medicine medicine Animals Humans Immunology and Allergy Transcription factor B cell Mice Knockout chemistry.chemical_classification Cell Differentiation Molecular biology DNA-Binding Proteins PPAR gamma B-1 cell Endocrinology medicine.anatomical_structure chemistry Organ Specificity Antibody Formation Proto-Oncogene Proteins c-bcl-6 biology.protein Positive Regulatory Domain I-Binding Factor 1 Antibody Transcription Factors |
| Zdroj: | The Journal of Immunology. 189:4740-4747 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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