Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues
Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues
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DOI：
10.1002/eji.201545586
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发表时间：
2016-02-01
影响因子：
5.4
通讯作者：
Barshack, Iris
中科院分区：
文献类型：
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作者：
Tabibian-Keissar, Hilla;Hazanov, Lena;Barshack, Iris
老年人免疫系统的特点是对感染和疫苗的反应减少，自身免疫性疾病和癌症的发病率增加。免疫系统中与年龄相关的缺陷可能是由于外周体内平衡压力限制了骨髓B细胞的产生或迁移到外周淋巴组织造成的。对外周血液B细胞受体谱型的研究表明，老年人的B细胞受体谱型的特征是多样性减少，这与健康状况不佳有关。在这项研究中，我们首次对老年人(74+/-7岁，范围6189)和年轻人(24+/-5岁，范围18-45)的初级和次级淋巴组织的存档活检样本中的免疫球蛋白基因进行了高通量测序，分析了谱系的多样性，并将这些结果与外周血中的结果进行了比较。我们发现老年人外周血和淋巴结谱的多样性降低，而老年脾样本的多样性大于年轻人。各年龄组间的体细胞高突变特征无差异。这些结果支持这样一种假设，即年龄相关的免疫脆弱源于B细胞稳态改变导致记忆B细胞谱系变窄，而不是体细胞超突变机制的改变。
The elderly immune system is characterized by reduced responses to infections and vaccines, and an increase in the incidence of autoimmune diseases and cancer. Age-related deficits in the immune system may be caused by peripheral homeostatic pressures that limit bone marrow B-cell production or migration to the peripheral lymphoid tissues. Studies of peripheral blood B-cell receptor spectratypes have shown that those of the elderly are characterized by reduced diversity, which is correlated with poor health status. In the present study, we performed for the first time high-throughput sequencing of immunoglobulin genes from archived biopsy samples of primary and secondary lymphoid tissues in old (74 +/- 7 years old, range 6189) versus young (24 +/- 5 years old, range 18-45) individuals, analyzed repertoire diversities and compared these to results in peripheral blood. We found reduced repertoire diversity in peripheral blood and lymph node repertoires from old people, while in the old spleen samples the diversity was larger than in the young. There were no differences in somatic hypermutation characteristics between age groups. These results support the hypothesis that age-related immune frailty stems from altered B-cell homeostasis leading to narrower memory B-cell repertoires, rather than changes in somatic hypermutation mechanisms.