Choi Jinwook, Jeon Shin, Choi Seungjin, Park Kyungsoo, Seong Rho Hyun
School of Biological Sciences and Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
School of Biological Sciences and Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):E718-27. doi: 10.1073/pnas.1418592112. Epub 2015 Feb 2.
Germinal center (GC) reaction is crucial in adaptive immune responses. The formation of GC is coordinated by the expression of specific genes including Blimp-1 and Bcl-6. Although gene expression is critically influenced by the status of chromatin structure, little is known about the role of chromatin remodeling factors for regulation of GC formation. Here, we show that the SWI/SNF chromatin remodeling complex is required for GC reactions. Mice lacking Srg3/mBaf155, a core component of the SWI/SNF complex, showed impaired differentiation of GC B and follicular helper T cells in response to T cell-dependent antigen challenge. The SWI/SNF complex regulates chromatin structure at the Blimp-1 locus and represses its expression by interacting cooperatively with Bcl-6 and corepressors. The defect in GC reactions in mice lacking Srg3 was due to the derepression of Blimp-1 as supported by genetic studies with Blimp-1-ablated mice. Hence, our study identifies the SWI/SNF complex as a key mediator in GC reactions by modulating Bcl-6-dependent Blimp-1 repression.
生发中心（GC）反应在适应性免疫应答中至关重要。GC的形成由包括Blimp-1和Bcl-6在内的特定基因的表达协调。尽管基因表达受到染色质结构状态的关键影响，但关于染色质重塑因子在调节GC形成中的作用知之甚少。在此，我们表明SWI/SNF染色质重塑复合体是GC反应所必需的。缺乏Srg3/mBaf155（SWI/SNF复合体的核心组分）的小鼠在受到T细胞依赖性抗原攻击时，GC B细胞和滤泡辅助性T细胞的分化受损。SWI/SNF复合体调节Blimp-1基因座处的染色质结构，并通过与Bcl-6和共抑制因子协同相互作用来抑制其表达。缺乏Srg3的小鼠中GC反应的缺陷是由于Blimp-1的去抑制，这得到了Blimp-1基因敲除小鼠的遗传学研究的支持。因此，我们的研究通过调节Bcl-6依赖性的Blimp-1抑制，将SWI/SNF复合体鉴定为GC反应中的关键介质。
