DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID.

TitleDNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID.
Publication TypeJournal Article
Year of Publication2015
AuthorsDominguez PM, Teater M, Chambwe N, Kormaksson M, Redmond D, Ishii J, Vuong B, Chaudhuri J, Melnick A, Vasanthakumar A, Godley LA, F Papavasiliou N, Elemento O, Shaknovich R
JournalCell Rep
Date Published2015 Sep 29
KeywordsAnimals, B-Lymphocytes, Cell Differentiation, Cell Movement, Cell Proliferation, Conserved Sequence, Cytidine Deaminase, Cytosine, DNA Methylation, Epigenesis, Genetic, Germinal Center, Humans, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Mice, Knockout

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.

Alternate JournalCell Rep
PubMed ID26365193
PubMed Central IDPMC4591215
Grant ListR01 CA194547 / CA / NCI NIH HHS / United States
1R01CA194547 / CA / NCI NIH HHS / United States