Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses
Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses
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DOI：
10.1073/pnas.0703872104
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发表时间：
2007-08-14
影响因子：
11.1
通讯作者：
Tangye, Stuart G.
中科院分区：
文献类型：
--
作者：
Good, Kim L.;Tangye, Stuart G.
二次抗体应答的特征在于应答细胞的快速动力学，包括与初次应答相比产生更大量的血清IG。记忆B细胞，这是负责这一现象，经历更大的增殖和分化为Ig分泌浆细胞比幼稚B细胞。我们已经发现，记忆细胞迅速进入细胞分裂，不管外界刺激。人类脾B细胞的微阵列分析显示，幼稚细胞表达高于记忆B细胞的Kruppel样因子（KLF）4、KLF 9和早幼粒细胞白血病锌指（PLZF），这些转录因子在维持细胞静止中很重要。这些基因在通过CD 40和B细胞受体活化后下调。记忆B细胞中KLF4、KLF9和PLZF的增强表达延迟了它们进入分裂并减少了增殖细胞的数量，使得转染的记忆细胞的行为类似于幼稚B细胞。因此，记忆B细胞的加速反应与KLF4、KLF9和PLZF的表达减少以及随后它们对细胞周期的调节作用相关。
Secondary antibody responses are characterized by the rapid kinetics of the responding cells, including the production of larger amounts of serum Ig compared with the primary response. Memory B cells, which are responsible for this phenomenon, undergo greater proliferation and differentiation into Ig-secreting plasma cells than naive B cells. We have found that memory cells rapidly enter cell division, irrespective of extrinsic stimuli. Microarray analysis of human splenic B cells revealed that naive cells express higher levels than memory B cells of Kruppel-like factor (KLF) 4, KLF9, and promyelocytic leukemia zinc finger (PLZF), transcription factors important in maintaining cellular quiescence. These genes were down-regulated after activation through CD40 and the B cell receptor. Enforced expression of KLF4, KLF9, and PLZF in memory B cells delayed their entry into division and reduced the number of proliferating cells, such that the behavior of transfected memory cells resembled that of naive B cells. Thus, the accelerated response of memory B cells correlates with reduced expression of KLF4, KLF9, and PLZF and the subsequent regulatory effects they exert on the cell cycle.