title: DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID.
abstract: Changes in DNA methylation are required for the formation of germinal centers (GCs), but the mechanisms of such changes are poorly understood. Activation-induced cytidine deaminase (AID) has been recently implicated in DNA demethylation through its deaminase activity coupled with DNA repair. We investigated the epigenetic function of AID in vivo in germinal center B cells (GCBs) isolated from wild-type (WT) and AID-deficient (Aicda(-/-)) mice. We determined that the transit of B cells through the GC is associated with marked locus-specific loss of methylation and increased methylation diversity, both of which are lost in Aicda(-/-) animals. Differentially methylated cytosines (DMCs) between GCBs and naive B cells (NBs) are enriched in genes that are targeted for somatic hypermutation (SHM) by AID, and these genes form networks required for B cell development and proliferation. Finally, we observed significant conservation of AID-dependent epigenetic reprogramming between mouse and human B cells.
authors.affiliation: Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Pilar M
authors.initials: PM
authors.lastname: Dominguez
authors.affiliation: Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, USA; Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Teater
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Nyasha
authors.initials: N
authors.lastname: Chambwe
authors.affiliation: IBM Research, Rio de Janeiro 22290-240, Brazil.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kormaksson
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: David
authors.initials: D
authors.lastname: Redmond
authors.affiliation: Epigenomics Core Facility, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ishii
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, Gerstner Sloan-Kettering Graduate School, New York, NY 10065, USA.
authors.forename: Bao
authors.initials: B
authors.lastname: Vuong
authors.affiliation: Immunology Program, Memorial Sloan-Kettering Cancer Center, Gerstner Sloan-Kettering Graduate School, New York, NY 10065, USA.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chaudhuri
authors.affiliation: Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Ari
authors.initials: A
authors.lastname: Melnick
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aparna
authors.initials: A
authors.lastname: Vasanthakumar
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Godley
authors.affiliation: Laboratories of Lymphocyte Biology and Molecular Parasitology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: F Nina
authors.initials: FN
authors.lastname: Papavasiliou
authors.affiliation: Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Division of Hematology and Oncology, Weill Cornell Medical College, New York, NY 10065, USA; Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: rshaknovich@gmail.com.
authors.forename: Rita
authors.initials: R
authors.lastname: Shaknovich
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D017124:Conserved Sequence; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D003596:Cytosine; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase