The control mechanism of B cells activation due to pKnox1 homeodomain transcription factor

在小鼠中，条件性B细胞特异性敲除pKnox1（一种同源结构域转录因子）可导致自身免疫表型的年龄相关发展。为了了解分子基础，我们分析了B细胞的发育和免疫反应。小鼠表现为边缘带B细胞发育异常，IgG水平下降，体细胞超突变频率降低导致亲和成熟延迟，生发中心形成延迟。与对照组相比，激活诱导胞苷脱氨酶（AID）的表达水平降低。直接调控AID表达的HoxC4表达水平也下降。我们在HoxC4启动子中也发现了与pKonox1-Pbx1复合物结合域相似的序列。这些发现提示，B细胞特异性敲除pKnox1小鼠的自身免疫表型可能与AID表达调控机制失效有关。

Conditional B cell-specific knockout of pKnox1, a homeodomain transcription factor, in mice leads to age-associated development of autoimmune phenotypes. In order to understand the molecular basis, we analyzed B cell development and immune responses. The mice showed abnormal marginal zone B cell development, decreased IgG level, delayed affinity maturation caused by decreased frequency of somatic hypermutation and delayed germinal center formation. The expression level of AID (Activation-induced cytidine deaminase) was decreased in the mice compared with control mice. The expression level of HoxC4 that directly regulates AID expression also decreased. We found the sequence that is similar to pKonox1-Pbx1 complex binding domain in HoxC4 promoter, too. These findings indicate that the autoimmune phenotypes in B cell–specific knockout of pKnox1 mice might be related to the failure of AID expression regulatory mechanisms.