title: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors.forename: Sesquile
authors.initials: S
authors.lastname: Ramon
authors.forename: Simona
authors.initials: S
authors.lastname: Bancos
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Thatcher
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Murant
authors.forename: Safiehkhatoon
authors.initials: S
authors.lastname: Moshkani
authors.forename: Julie M
authors.initials: JM
authors.lastname: Sahler
authors.forename: Andrea
authors.initials: A
authors.lastname: Bottaro
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sime
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D000917:Antibody Formation / Q000502:physiology*; D000918:Antibody Specificity / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology*; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D047495:PPAR gamma; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1