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Compromised steady-state germinal center activity with age in nonhuman primates.
Aging Cell ( IF 7.8 ) Pub Date : 2019-12-15 , DOI: 10.1111/acel.13087
Kimberly Shankwitz 1, 2 , Suresh Pallikkuth 3 , Tirupataiah Sirupangi 2 , Daniel Kirk Kvistad 3 , Kyle Blaine Russel 3 , Rajendra Pahwa 3 , Lucio Gama 4, 5, 6 , Richard A Koup 6 , Li Pan 3 , Francois Villinger 2 , Savita Pahwa 3 , Constantinos Petrovas 1
Affiliation  

Age‐related reductions in vaccine‐induced B cells in aging indicate that germinal centers (GCs), the anatomical site where the development of humoral responses takes place, may lose efficacy with age. We have investigated the baseline follicular and GC composition in nonhuman primates (NHPs) with respect to their age. There was a marked reduction in follicular area in old animals. We found significantly lower normalized numbers of follicular PD1hi CD4 T (Tfh) and proliferating (Ki67hi) GC B cells with aging, a profile associated with significantly higher numbers of potential follicular suppressor FoxP3hiLag3hi CD4 T cells. Furthermore, a positive correlation was found between Tfh and follicular CD8 T cells (fCD8) only in young animals. Despite the increased levels of circulating preinflammatory factors in aging, young animals had higher numbers of monocytes and granulocytes in the follicles, a profile negatively associated with numbers of Tfh cells. Multiple regression analysis showed an altered association between GC B cells and other GC immune cell populations in old animals suggesting a differential mechanistic regulation of GC activity in aging. Our data demonstrate defective baseline GC composition in old NHPs and provide an immunological base for further understanding the adaptive humoral responses with respect to aging.

中文翻译:

非人灵长类动物的稳态生发中心活动随着年龄的增长而受损。

疫苗诱导的 B 细胞在衰老过程中与年龄相关的减少表明,生发中心 (GCs) 是发生体液反应的解剖部位,可能会随着年龄的增长而失效。我们调查了非人灵长类动物 (NHP) 的基线卵泡和 GC 组成与年龄的关系。老年动物的毛囊面积明显减少。我们发现随着衰老,滤泡 PD1 hi CD4 T (Tfh) 和增殖 (Ki67 hi ) GC B 细胞的归一化数量显着降低,这一特征与潜在滤泡抑制因子 FoxP3 hi Lag3 hi的数量显着增加相关CD4 T 细胞。此外,仅在幼小动物中发现 Tfh 和滤泡 CD8 T 细胞 (fCD8) 之间呈正相关。尽管在衰老过程中循环的前炎症因子水平增加,但年轻动物的卵泡中单核细胞和粒细胞数量增加,这与 Tfh 细胞数量呈负相关。多元回归分析显示,老年动物的 GC B 细胞与其他 GC 免疫细胞群之间的关联发生了改变,这表明 GC 活性在衰老过程中存在不同的机制调节。我们的数据证明了旧 NHP 中有缺陷的基线 GC 组成,并为进一步了解与衰老相关的适应性体液反应提供了免疫学基础。
更新日期:2019-12-15
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