T regulatory cells participate in the control of germinal centre reactions
T regulatory cells participate in the control of germinal centre reactions
复制标题
DOI：
10.1111/j.1365-2567.2011.03456.x
复制
发表时间：
2011-08-01
期刊：
影响因子：
6.4
通讯作者：
Waldschmidt, Thomas J.
中科院分区：
文献类型：
--
作者：
Alexander, Carla-Maria;Tygrett, Lorraine T.;Waldschmidt, Thomas J.
生发中心（GC）反应是t细胞驱动的B细胞反应的核心特征，也是产生抗体细胞和记忆B细胞的部位。在GCs中，发生了一系列复杂的细胞和分子事件，这些事件对于产生高亲和力抗体至关重要。这些过程需要精细的调节，不仅要确保所需抗体的产生，而且要尽量减少不需要的自反应性或低亲和力抗体。为了评估T调节性（Treg）细胞是否参与GC反应的控制，免疫小鼠使用抗糖皮质激素诱导的肿瘤坏死因子受体相关蛋白（GITR）单克隆抗体（mAb）来破坏Treg细胞的活性。在抗gitr处理的小鼠中，与对照处理的动物相比，GC B细胞池明显更大，切换的GC B细胞在应答中所占比例异常高。无论菌株、辅助性T型1或2极化抗原如何，也可以观察到异常的GCs，并且在抗cd25单抗治疗后也可以观察到。免疫小鼠脾脏内，流式细胞术检测到CXCR5（+）和CCR7(-) Treg细胞，免疫组织学检测到GCs内Foxp3（+）细胞。最后的研究表明，抗转化生长因子- β或抗白细胞介素-10受体阻断单抗同样会导致GC失调，这表明诱导Treg细胞的产生对控制GC反应很重要。综上所述，这些发现表明Treg细胞通过控制GCs内的稳态来影响体液反应的总体大小和质量。
Germinal centre (GC) reactions are central features of T-cell-driven B-cell responses, and the site where antibody-producing cells and memory B cells are generated. Within GCs, a range of complex cellular and molecular events occur which are critical for the generation of high affinity antibodies. These processes require exquisite regulation not only to ensure the production of desired antibodies, but to minimize unwanted autoreactive or low affinity antibodies. To assess whether T regulatory (Treg) cells participate in the control of GC responses, immunized mice were treated with an anti-glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) monoclonal antibody (mAb) to disrupt Treg-cell activity. In anti-GITR-treated mice, the GC B-cell pool was significantly larger compared with control-treated animals, with switched GC B cells composing an abnormally high proportion of the response. Dysregulated GCs were also observed regardless of strain, T helper type 1 or 2 polarizing antigens, and were also seen after anti-CD25 mAb treatment. Within the spleens of immunized mice, CXCR5(+) and CCR7(-) Treg cells were documented by flow cytometry and Foxp3(+) cells were found within GCs using immunohistology. Final studies demonstrated administration of either anti-transforming growth factor-beta or anti-interleukin-10 receptor blocking mAb to likewise result in dysregulated GCs, suggesting that generation of inducible Treg cells is important in controlling the GC response. Taken together, these findings indicate that Treg cells contribute to the overall size and quality of the humoral response by controlling homeostasis within GCs.