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Plant homeodomain finger protein 11 promotes class switch recombination to IgE in murine activated B cells
Author(s) -
Ikari J.,
Inamine A.,
Yamamoto T.,
WatanabeTakano H.,
Yoshida N.,
Fujimura L.,
Taniguchi T.,
Sakamoto A.,
Hatano M.,
Tatsumi K.,
Tokuhisa T.,
Arima M.
Publication year - 2014
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12328
Subject(s) - immunoglobulin e , immunoglobulin class switching , microbiology and biotechnology , gene silencing , ovalbumin , cd23 , transgene , chemistry , biology , immunology , immune system , antibody , gene , b cell , biochemistry
Background Polymorphisms of the Plant homeodomain finger protein 11 ( PHF 11 ) 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 ) γ 1 and GLT ε expression. The exogenous Phf11 augmented transcriptional activity of the GLT γ 1 and GLT ε promoters through permissive histone modifications and binding of NF ‐κB and STAT 6. 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 γ 1 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. Conclusion 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.