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

Authors :: Dominguez PM
Teater M
Chambwe N
Kormaksson M
Redmond D
Ishii J
Vuong B
Chaudhuri J
Melnick A
Vasanthakumar A
Godley LA
Papavasiliou FN
Elemento O
Shaknovich R
Source :: Cell reports [Cell Rep] 2015 Sep 29; Vol. 12 (12), pp. 2086-98. Date of Electronic Publication: 2015 Sep 10.
Publication Year :: 2015
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.<br /> (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)