Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095;
J Immunol. 2014 May 1;192(9):4069-73. doi: 10.4049/jimmunol.1302897. Epub 2014 Mar 26.
To prevent autoimmunity, anergy of autoreactive B cells needs to be maintained, together with the suppression of hyperactive B cells. We previously reported that CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) can directly suppress autoantibody-producing autoreactive B cells in systemic lupus erythematosus. In this article, we show that Tregs can also reduce the production of autoantibodies in (NZB × NZW)F1 mouse lupus B cells by promoting B cell anergy, both in vitro and in vivo. This phenomenon associated with a reduction in Ca(2+) flux in B cells, and CTLA-4 blockade inhibited the effects of Tregs on anergic lupus B cells. These findings identify a new mechanism by which Tregs can control production of autoantibodies in lupus B cells and, more generally, B cell activity in physiopathological conditions.
为了预防自身免疫，需要维持自身反应性 B 细胞的无反应性，同时抑制过度活跃的 B 细胞。我们之前报道过，CD4(+)CD25(+)Foxp3(+)调节性 T 细胞（Tregs）可以直接抑制系统性红斑狼疮中的自身抗体产生的自身反应性 B 细胞。在本文中，我们表明 Tregs 还可以通过促进 B 细胞无反应性，在体外和体内减少（NZB×NZW）F1 狼疮小鼠 B 细胞产生的自身抗体。这种现象与 B 细胞中 Ca(2+)流的减少有关，并且 CTLA-4 阻断抑制了 Tregs 对无反应性狼疮 B 细胞的作用。这些发现确定了 Tregs 可以控制狼疮 B 细胞中自身抗体产生的新机制，更普遍地说，还确定了 Tregs 可以控制生理病理条件下 B 细胞活性的新机制。
