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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Anti-Idiotypic / pharmacology
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Antibodies, Monoclonal / pharmacology
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology*
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Cell Differentiation
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Gene Knockout Techniques
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Germinal Center / cytology
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Germinal Center / immunology*
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Immunoglobulin G / blood
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Immunoglobulin G / genetics
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / metabolism
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Integrases / genetics
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Integrases / metabolism
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Lymphocyte Activation
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Mice
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Mice, Transgenic
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Precursor Cells, B-Lymphoid / cytology
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Precursor Cells, B-Lymphoid / immunology*
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Promoter Regions, Genetic
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Spleen / cytology
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Spleen / immunology*
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YY1 Transcription Factor / deficiency
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YY1 Transcription Factor / genetics*
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YY1 Transcription Factor / immunology
Substances
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Antibodies, Anti-Idiotypic
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Antibodies, Monoclonal
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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YY1 Transcription Factor
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Yy1 protein, mouse
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anti-IgM
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Cre recombinase
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Integrases