The transcriptional programme of antibody class switching involves the repressor Bach2

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Abstract

Activated B cells differentiate to plasma cells to secrete IgM or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins1-4. 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 stage5-7. Here we show that Bach2 is critical for CSR and somatic hypermutation (SHM)2,4,8of immunoglobulin genes. Genetic ablation ofBach2in mice revealed that Bach2 was required for both T-cell-independent and T-cell-dependent IgG responses and SHM. When stimulatedin vitro,Bach2-deficient B cells produced IgM, as did wild-type cells, and abundantly expressed Blimp-1 (refs9, 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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