title: YY1 Is Required for Germinal Center B Cell Development.
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.
authors.affiliation: Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Anupam
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Vishal
authors.initials: V
authors.lastname: Sindhava
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, 233 South Tenth Street, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Raja
authors.initials: R
authors.lastname: Vuyyuru
authors.affiliation: Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Vibha
authors.initials: V
authors.lastname: Jha
authors.affiliation: Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Suchita
authors.initials: S
authors.lastname: Hodewadekar
authors.affiliation: Department of Microbiology and Immunology, Thomas Jefferson University, 233 South Tenth Street, Philadelphia, Pennsylvania 19107, United States of America.
authors.forename: Tim
authors.initials: T
authors.lastname: Manser
authors.affiliation: Department of Biomedical Sciences, University of Pennsylvania, School of Veterinary Medicine, 3800 Spruce Street, Philadelphia, Pennsylvania 19104, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Atchison
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D055786:Gene Knockout Techniques; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology*; D011401:Promoter Regions, Genetic; D013154:Spleen / Q000166:cytology / Q000276:immunology*; D050986:YY1 Transcription Factor / Q000172:deficiency / Q000235:genetics* / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; C044203:anti-IgM; C045073:Cre recombinase; D019426:Integrases