Muto, A. et al. The transcriptional programme of antibody class switching involves the repressor Bach2. Nature 429, 566-571

Department of Biomedical Chemistry and Leukemia Program Project, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima 734-8551, Japan.
Nature (Impact Factor: 41.46). 07/2004; 429(6991):566-71. DOI: 10.1038/nature02596
Source: PubMed


Activated B cells differentiate to plasma cells to secrete 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 before the plasma cell stage. Here we show 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 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 differentiation, 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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    • "Restifo and colleagues very recently reported a novel role of the transcriptional repressor BACH2 in regulating Treg differentiation and decreasing the effector function of Th1 and Th17 cells (123). BACH2 is a known regulator of Blimp-1 in B cells required for class switch recombination; however, its role in T cells was unknown (124). When CD4+ T cells were programed toward an inducible Treg subset (via IL-2 and TGF-β), wild-type cells converted to FoxP3+ Treg cells while Bach2 KO cells differentiated into effector T cells (Figure 6A). "
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    • "Mice. Bach2-deficient mice were described previously (Muto et al., 2004). B cell–specific Blimp-1–deficient mice (Shapiro-Shelef et al., 2003) were provided by K. "
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    • "This gene transcribes the BACH2 protein that has high expression in B cells prior to the plasma cell stage of B cell development (Muto et al., 2004). BACH2 is a critical player in class switch recombination and somatic hypermutation (Muto et al., 2004). Little more is known about the mechanisms by which this association operates. "
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