title: Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells.
abstract: BACKGROUND
  Polymorphisms of the Plant homeodomain finger protein 11 (PHF11) are strongly associated with high serum IgE levels and clinical severity of atopic patients. However, the precise mechanism has not been fully elucidated. We investigated the role of Phf11 in class switch recombination (CSR) to IgE by activated B cells.
  
  
  METHODS
  We generated Phf11 transgenic (Lckd-Phf11-Tg) mice that express the exogenous murine Phf11 in lymphocytes under the control of distal Lck promoter. We examined IL-4-induced CSR to IgE in activated Lckd-Phf11-Tg B cells in vitro. We analyzed production of ovalbumin (OVA)-specific IgE and nose-scratching symptoms in Lckd-Phf11-Tg mice using an OVA-induced allergic rhinitis model.
  
  
  RESULTS
  The exogenous Phf11 promoted CSR to IgG1 and IgE in activated B cells with an increase in germ line transcript (GLT) γ1 and GLT ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT γ1 and GLT ε promoters through permissive histone modifications and binding of NF-κB and STAT6. Furthermore, the exogenous Phf11 bound to the GLT ε promoter with increased binding of NF-κB. Silencing of the endogenous Phf11 reduced the frequency of CSR to IgE and GLT ε expression, but not to IgG1 or GLT γ1 expression, in activated B cells. In an allergic rhinitis model, Lckd-Phf11-Tg mice showed a significant increase in the production of OVA-specific IgE and the frequency of nose scratching.
  
  
  CONCLUSIONS
  Phf11 accelerates CSR to IgE in activated B cells by increasing the transcriptional activity of GLT ε promoter and contributes to the exacerbation of allergic responses. These findings provide a novel therapeutic target for allergic diseases.
authors.affiliation: Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Respirology (B2), Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Ikari
authors.forename: A
authors.initials: A
authors.lastname: Inamine
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: H
authors.initials: H
authors.lastname: Watanabe-Takano
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: L
authors.initials: L
authors.lastname: Fujimura
authors.forename: T
authors.initials: T
authors.lastname: Taniguchi
authors.forename: A
authors.initials: A
authors.lastname: Sakamoto
authors.forename: M
authors.initials: M
authors.lastname: Hatano
authors.forename: K
authors.initials: K
authors.lastname: Tatsumi
authors.forename: T
authors.initials: T
authors.lastname: Tokuhisa
authors.forename: M
authors.initials: M
authors.lastname: Arima
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000276:immunology*; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology
chemical_list: D018398:Homeodomain Proteins; D007073:Immunoglobulin E
keywords: IgE; NF-κB; allergy; class switch recombination; plant homeodomain finger protein 11