Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
J Exp Med. 2011 Nov 21;208(12):2497-510. doi: 10.1084/jem.20111449. Epub 2011 Oct 31.
Follicular dendritic cells (FDCs) retain and display opsonized antigens in primary follicles and germinal centers (GCs). However, their roles beyond antigen presentation have been incompletely defined. In this study, we tested the impact of selective FDC ablation on short-term follicle and GC function. Within 2 d of FDC ablation, primary follicles lost their homogeneity and became disorganized bands of cells around T zones. These B cell areas retained CXCL13-expressing stromal cells but often exhibited inappropriate ER-TR7 and CCL21 expression. Ablation of GC FDCs led to the disappearance of GCs. When B cell death was prevented using a Bcl2 transgene, FDC ablation led to splenic GC B cell dispersal. Mesenteric lymph node GCs were more resistant but became dispersed when sphingosine-1-phosphate receptor-2 was also removed. These experiments indicate that FDCs help maintain primary follicles as a B cell exclusive niche and define a critical role for FDCs in cell retention within GCs.
滤泡树突状细胞(FDC)在初级滤泡和生发中心(GC)中保留和展示被调理的抗原。然而,它们在抗原呈递之外的作用尚未完全确定。在这项研究中,我们测试了选择性 FDC 消融对短期滤泡和 GC 功能的影响。在 FDC 消融后 2 天内,初级滤泡失去了其同质性,变成了围绕 T 区的细胞不整齐的带。这些 B 细胞区仍然保留表达 CXCL13 的基质细胞,但常常表现出不合适的 ER-TR7 和 CCL21 表达。GC FDC 的消融导致 GC 的消失。当使用 Bcl2 转基因阻止 B 细胞死亡时,FDC 消融导致脾脏 GC B 细胞分散。肠系膜淋巴结 GC 更具抗性,但当同时去除鞘氨醇-1-磷酸受体-2 时也会分散。这些实验表明,FDC 有助于将初级滤泡维持为 B 细胞的专有龛位,并确定了 FDC 在 GC 内细胞保留中的关键作用。