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

The transcription factor Bach2 is required for germinal center formation and somatic hypermutation (SHM) of immunoglobulins, both central to an efficient antibody-mediated immune response. Activation-induced cytidine deaminase (AID) initiates SHM and CSR in germinal centers and 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), an important 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. These results demonstrate that Bach2 has a previously unappreciated role in the production of high-affinity antibodies. Overall design: Gene expression profiles of Clone 18 (Wild type) and Bach2 knockout (Bach2KO) chicken DT40 B cells were generated by deep sequencing, in triplicate, using Illumina HiSeq2500 instrument and paired-end sequencing chemistry with 100bp read length

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Budzyńska PM, Kyläniemi MK, Kallonen T, Soikkeli AI, Nera KP, Lassila O, Alinikula J