Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells

[thumbnail of Original Article]
Preview
PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB

Item Type:Article
Title:TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells
Creators Name:Schoeler, K., Aufschnaiter, A., Messner, S., Derudder, E., Herzog, S., Villunger, A., Rajewsky, K. and Labi, V.
Abstract:Upon activation by antigen, B cells form germinal centers where they clonally expand and introduce affinity-enhancing mutations into their B cell receptor genes. Somatic mutagenesis and class switch recombination in germinal center B cells are initiated by the activation-induced cytidine deaminase (AID). Upon germinal center exit, B cells differentiate into antibody-secreting plasma cells. Germinal center maintenance and terminal fate choice require transcriptional reprogramming that associates with a substantial reconfiguration of DNA methylation patterns. Here we examine the role of TET proteins, enzymes that facilitate DNA demethylation and promote a permissive chromatin state by oxidizing 5-methylcytosine, in antibody-mediated immunity. Using a conditional gene ablation strategy, we show that TET2 and TET3 guide the transition of germinal center B cells to antibody-secreting plasma cells. Optimal AID expression requires TET function, and TET2 and TET3 double-deficient germinal center B cells show defects in class switch recombination. However, TET2/TET3 double-deficiency does not prevent the generation and selection of high-affinity germinal center B cells. Rather, combined TET2 and TET3 loss-of-function in germinal center B cells favors C-to-T and G-to-A transition mutagenesis, a finding that may be of significance for understanding the etiology of B cell lymphomas evolving in conditions of reduced TET function.
Keywords:B Cells, Germinal Center, Somatic Hypermutation, TET2, TET3, Animals, Mice
Source:FEBS Journal
ISSN:1742-464X
Publisher:Wiley
Volume:286
Number:18
Page Range:3566-3581
Date:September 2019
Official Publication:https://doi.org/10.1111/febs.14934
PubMed:View item in PubMed

Repository Staff Only: item control page

Downloads

Downloads per month over past year

Open Access
MDC Library