奥地利分子病理学研究所Meinrad Busslinger和Tanja A. Schwickert研究组合作研究显示，Ikaros通过控制B细胞的衰老和toll样受体(TLR)信号来防止自身免疫。相关论文2019年10月7日在线发表在《自然—免疫学》杂志上。

他们描述了转录因子Ikaros在控制B细胞抗原受体（BCR）无能和TLR信号传导中的关键作用。成熟B细胞中Ikaros特异缺失的小鼠患有系统自身免疫性疾病。Ikaros调节了许多与无能相关的基因，包括Zfp318，该基因通过促进无能B细胞中免疫球蛋白D的表达而减弱了BCR的反应能力。在Ikaros缺陷型B细胞中，TLR信号活跃，该细胞不能上调MyD88-NFκB信号通路的反馈抑制性。在Ikaros缺陷的B细胞中表达非自我反应性BCR或MyD88缺失时，系统性炎症消失。

因此，Ikaros通过促进BCR无能和抑制TLR信号传导来防止自身免疫。

研究人员表示，通过V（D）J重组建立多样化的BCR也可产生自反应性B细胞。无能是一种耐受机制；它使自身反应性B细胞对自身抗原的刺激不敏感，而TLR信号传导可以重新激活衰老B细胞。

附：英文原文

Title: Ikaros prevents autoimmunity by controlling anergy and Toll-like receptor signaling in B cells

Author: Tanja A. Schwickert, Hiromi Tagoh, Karina Schindler, Maria Fischer, Markus Jaritz, Meinrad Busslinger

Issue&Volume: 2019-10-07

Abstract: 

The establishment of a diverse B cell antigen receptor (BCR) repertoire by V(D)J recombination also generates autoreactive B cells. Anergy is one tolerance mechanism; it renders autoreactive B cells insensitive to stimulation by self-antigen, whereas Toll-like receptor (TLR) signaling can reactivate anergic B cells. Here, we describe a critical role of the transcription factor Ikaros in controlling BCR anergy and TLR signaling. Mice with specific deletion of Ikaros in mature B cells developed systemic autoimmunity. Ikaros regulated many anergy-associated genes, including Zfp318, which is implicated in the attenuation of BCR responsiveness by promoting immunoglobulin D expression in anergic B cells. TLR signaling was hyperactive in Ikaros-deficient B cells, which failed to upregulate feedback inhibitors of the MyD88–nuclear factor κB signaling pathway. Systemic inflammation was lost on expression of a non-self-reactive BCR or loss of MyD88 in Ikaros-deficient B cells. Thus, Ikaros acts as a guardian preventing autoimmunity by promoting BCR anergy and restraining TLR signaling.

DOI: 10.1038/s41590-019-0490-2

Source: https://www.nature.com/articles/s41590-019-0490-2