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PLoS One ; 11(5): e0155311, 2016.
Article in English | MEDLINE | ID: mdl-27167731

ABSTRACT

YY1 has been implicated as a master regulator of germinal center B cell development as YY1 binding sites are frequently present in promoters of germinal center-expressed genes. YY1 is known to be important for other stages of B cell development including the pro-B and pre-B cells stages. To determine if YY1 plays a critical role in germinal center development, we evaluated YY1 expression during B cell development, and used a YY1 conditional knock-out approach for deletion of YY1 in germinal center B cells (CRE driven by the immunoglobulin heavy chain γ1 switch region promoter; γ1-CRE). We found that YY1 is most highly expressed in germinal center B cells and is increased 3 fold in splenic B cells activated by treatment with anti-IgM and anti-CD40. In addition, deletion of the yy1 gene by action of γ1-CRE recombinase resulted in significant loss of GC cells in both un-immunized and immunized contexts with corresponding loss of serum IgG1. Our results show a crucial role for YY1 in the germinal center reaction.


Subject(s)
B-Lymphocytes/immunology , Germinal Center/immunology , Precursor Cells, B-Lymphoid/immunology , Spleen/immunology , YY1 Transcription Factor/genetics , Animals , Antibodies, Anti-Idiotypic/pharmacology , Antibodies, Monoclonal/pharmacology , B-Lymphocytes/cytology , Cell Differentiation , Gene Knockout Techniques , Germinal Center/cytology , Immunoglobulin G/blood , Immunoglobulin G/genetics , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/metabolism , Integrases/genetics , Integrases/metabolism , Lymphocyte Activation , Mice , Mice, Transgenic , Precursor Cells, B-Lymphoid/cytology , Promoter Regions, Genetic , Spleen/cytology , YY1 Transcription Factor/deficiency , YY1 Transcription Factor/immunology
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