B cell Sirt1 deacetylates histone and non-histone proteins for epigenetic modulation of AID expression and the antibody response.

ABSTRACT: Activation-induced cytidine deaminase (AID) mediates immunoglobulin class switch DNA recombination (CSR) and somatic hypermutation (SHM), critical processes for maturation of the antibody response. Epigenetic factors, such as histone deacetylases (HDACs), would underpin B cell differentiation stage-specific AID expression. Here, we showed that NAD⁺-dependent class III HDAC sirtuin 1 (Sirt1) is highly expressed in resting B cells and down-regulated by stimuli inducing AID. B cell Sirt1 down-regulation, deprivation of NAD⁺ cofactor, or genetic Sirt1 deletion reduced deacetylation of Aicda promoter histones, Dnmt1, and nuclear factor-κB (NF-κB) p65 and increased AID expression. This promoted class-switched and hypermutated T-dependent and T-independent antibody re

SUBMITTER: Gan H 

PROVIDER: S-EPMC7112761 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature