Regulation of hematopoiesis by the transcription factors Bach1 and Bach2

点击翻译按钮获取中文摘要

For the sake of clarity, I shall give a summary of the analysis of B cell system below.Activated B cells differentiate to plasma cells to secrete immunoglobulin MI (IgM) or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins. Diversification of antibody function by CSR is important for humoral immunity. However, it remains unclear how the decision for the bifurcation is made. Bach2 is a B cell-specific transcription repressor interacting with the small Maf proteins whose expression is high only prior to plasma cell stage. Here we report that Bach2 is critical for CSR and somatic hypermutation (SHM) of immunoglobulin genes. Genetic ablation of bach2 in mice revealed that Bach2 was required for both T cell-independent and -dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM as did wild-type cells and expressed abundantly Blimp-1 and XBP-1, critical regulators of the plasmacytic differentiation, suggesting that Bach2 was not required for the plasmacytic differentiation per se. However, they failed to undergo efficient CSR. These findings define Bach2 as a key regulator of antibody response and provide an insight into the orchestration of CSR and SHM during plasma cell differentiation.