1. Department of Biomedical Chemistry and Leukemia Program Project, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan
2. Research Laboratory for Molecular Genetics, Yamagata University, Yamagata 990-9585, Japan
3. Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8577, Japan
4. Center for Tsukuba Advanced Research Alliance and Exploratory Research for Advanced Technology, Environmental Response Project, University of Tsukuba, Tsukuba 305-8577, Japan
5. Present address: National Institute of Advanced Industrial Science and Technology, Age Dimension Research Centre, Tsukuba 305-8566, Japan

Correspondence to: Kazuhiko Igarashi¹ Email: igarak@hiroshima-u.ac.jp

Abstract

Activated B cells differentiate to plasma cells to secrete IgM or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins^{1, 2, 3, 4}. 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 before the plasma cell stage^{5, 6, 7}. Here we show that Bach2 is critical for CSR and somatic hypermutation (SHM)^{2, 4, 8} of immunoglobulin genes. Genetic ablation of Bach2 in mice revealed that Bach2 was required for both T-cell-independent and T-cell-dependent IgG responses and SHM. When stimulated in vitro, Bach2-deficient B cells produced IgM, as did wild-type cells, and abundantly expressed Blimp-1 (refs 9, 10) and XBP-1 (ref. 11), critical regulators of the plasmacytic differentiation¹², indicating that Bach2 was not required for the plasmacytic differentiation itself. 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.

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