Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells

Abstract

The transcription factor Bach2 is required for germinal center formation, somatic hypermutation (SHM), and class‐switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation‐induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID‐mediated immunoglobulin gene diversification processes, we established a BACH2‐deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID‐dependent antibody gene diversification process. We demonstrate that Bach2 promotes GCV by increasing the expression of AID. Importantly, we found that the regulation of AID is independent of Blimp‐1 and that BACH2‐deficient cells have altered expression of several genes regulating AID expression, stability and function. Furthermore, re‐expression of BACH2 or AID in Bach2KO cells restored the SHM and GCV defects. These results demonstrate that Bach2 has a previously unappreciated role in the production of high‐affinity antibodies.