title: Overexpression of Bovine FcRn in Mice Enhances T-Dependent Immune Responses by Amplifying T Helper Cell Frequency and Germinal Center Enlargement in the Spleen.
abstract: The neonatal Fc receptor (FcRn) plays key roles in IgG and albumin homeostasis, maternal IgG transport, and antigen presentation of IgG-opsonized antigens. Previously, we reported that transgenic (Tg) mice that overexpress the bovine FcRn (bFcRn) have augmented T-dependent humoral immune response with increased IgG protection, higher level of antigen-specific antibodies, greater number of antigen-specific B cells, and effective immune response even against weakly immunogenic epitopes. In the current study, we analyzed the localization of the bFcRn in secondary lymphoid organs, and focused to demonstrate the in vivo impact of its overexpression in the spleen on the course of antibody production. bFcRn was highly expressed by red pulp macrophages and marginal zone macrophages in the spleen and by subcapsular sinus macrophages and macrophage-like cells in the interfollicular areas in the lymph node cortex. We also demonstrated that splenic dendritic cells of Tg mice express bFcRn and intraperitoneal immunization of these mice with T-dependent antigens led to more than threefold increase in the number of antigen-specific activated T helper cells with increased size and numbers of germinal centers compared to wild-type controls. bFcRn expression in splenic B cells was also detected and that may also contribute to the enhanced B cell activation. Finally, we demonstrated that these Tg mice developed efficient immune response against very low dose of antigen, reflecting another important practical benefit of these Tg mice.
authors.affiliation: Department of Immunology, Eötvös Loránd University , Budapest , Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Schneider
authors.affiliation: ImmunoGenes Kft , Budakeszi , Hungary.
authors.forename: Péter Károly
authors.initials: PK
authors.lastname: Jani
authors.affiliation: Department of Immunology, Eötvös Loránd University , Budapest , Hungary.
authors.forename: Bence
authors.initials: B
authors.lastname: Szikora
authors.affiliation: Department of Immunology, Eötvös Loránd University , Budapest , Hungary ; ImmunoGenes Kft , Budakeszi , Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Végh
authors.affiliation: Department of Immunology, Eötvös Loránd University , Budapest , Hungary.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Kövesdi
authors.affiliation: Department of Immunology, Eötvös Loránd University , Budapest , Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Iliás
authors.affiliation: ImmunoGenes Kft , Budakeszi , Hungary.
authors.forename: Judit
authors.initials: J
authors.lastname: Cervenak
authors.affiliation: Department of Immunology and Biotechnology, Medical School, University of Pécs , Pécs , Hungary ; Lymphoid Organogenesis Research Group, Szentágothai Research Center, University of Pécs , Pécs , Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Balogh
authors.affiliation: ImmunoGenes-ABS Zrt , Budapest , Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Kurucz
authors.affiliation: Department of Immunology, Eötvös Loránd University , Budapest , Hungary ; ImmunoGenes Kft , Budakeszi , Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Kacskovics
keywords: FcRn overexpression; antigen presentation; germinal center; humoral immune response