Department of Molecular Pathology, Institute of Pathology and 4 Comprehensive Cancer Center Mainfranken, Julius-Maximilians-University of Wuerzburg, 97080 Wuerzburg, Germany.
J Exp Med. 2014 Mar 10;211(3):545-61. doi: 10.1084/jem.20130604. Epub 2014 Mar 3.
Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4(+)CXCR5(+) follicular helper T cells (TFH) and inhibited by CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells.
高亲和力 B 淋巴细胞的成熟在生发中心反应中受到精确调控。这依赖于 CD4(+)CXCR5(+)滤泡辅助性 T 细胞（TFH），并受到 CD4(+)CXCR5(+)Foxp3(+)滤泡调节性 T 细胞（TFR）的抑制。由于发现 NFAT2 在滤泡 T 细胞中高度表达和激活，我们在此研究其功能。出乎意料的是，T 细胞中 NFAT2 的缺失导致免疫后 GC 反应增强。然而，一致的是，由于向 B 细胞滤泡归巢受损，TFR 细胞在滤泡 T 细胞群体中明显减少。这是 TFR 细胞内在的，因为只有在这些细胞中，NFAT2 对于上调 CXCR5 是必需的。NFAT2 缺陷的 TFR 细胞存在时，体液（自身）免疫的生理相关性得到了验证，表现为狼疮样疾病加重。
