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: 42.35). 07/2004; 429(6991):566-71. DOI: 10.1038/nature02596
Source: PubMed

ABSTRACT 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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Available from: Dai Ikebe, Feb 12, 2015
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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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    • "promoter of TRPV2 shows binding sites for regulatory transcription factors such as AP2rep, NF-AT1, NF-AT2, and NF-AT3 as well as for Bach-2 (Su et al., 2004), which is critical for class switch recombination and somatic hypermutation of immunoglobulin genes (Muto et al., 2004). TRPV2 channel has been found to be associated with the recombinase gene activator protein during biosynthesis and early trafficking; it has been observed that over-expression of RGA protein potentiates basal surface localization of TRPV2 and cyclic adenosine monophosphate (cAMP) signal in human non-sensory cells (Barnhill et al., 2004; Stokes et al., 2005). "
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