Abstract：
B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region, and class switching of the Igh constant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for the successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an open chromatin state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacked both GCN5 and PCAF in B cells. Double-deficient mice possessed low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We concluded that both GCN5 and PCAF are required for B-cell development in vivo.
摘要：
B淋巴细胞发育有两个DNA重组过程：免疫球蛋白（Igh）基因可变区的V（D）J重组，以及从IgM到IgG的Igh恒定区的类别转换，IgA,或IgE。V（D）J重组是B细胞从pro-B到pre-B到未成熟B，然后在骨髓中成熟B细胞的成功成熟所必需的。当成熟B细胞迁移到外周淋巴器官时，CSR发生在骨髓外，如脾脏和淋巴结。V（D）J重组和CSR都依赖于开放的染色质状态，使DNA可以被特定的酶所接近。重组激活基因（RAG），和活化诱导的胞苷脱氨酶(AID)。乙酰转移酶GCN5和PCAF具有冗余的乙酰化组蛋白H3赖氨酸9(H3K9)的功能。这里,我们产生了在B细胞中缺乏GCN5和PCAF的小鼠模型。双缺陷小鼠在骨髓和外周器官中具有低水平的成熟B细胞，骨髓中pro-B细胞的积累,降低企业社会责任水平。我们得出结论，GCN5和PCAF都是体内B细胞发育所必需的。
