The transcriptional programme of antibody class switching involves the repressor Bach2

Article

关键词: PLASMA-CELL DIFFERENTIATION;    GERMINAL-CENTER FORMATION;    SMALL MAF PROTEINS;    SOMATIC HYPERMUTATION;    MATURE B;    RECOMBINATION;    MECHANISM;    BLIMP-1;    EXPRESSION;    ACTIVATION;   

DOI  :  10.1038/nature02596

来源: SCIE

【 摘 要 】

Activated B cells differentiate to plasma cells to secrete IgM or, after undergoing class switch recombination (CSR), to secrete other classes of immunoglobulins(1-4). 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(5-7). 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 differentiation(12), 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.

【 授权许可】

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