Department of Pathology, Stanford University, Stanford, CA 94305;
J Immunol. 2014 Jan 15;192(2):603-11. doi: 10.4049/jimmunol.1301384. Epub 2013 Dec 11.
Elderly humans show decreased humoral immunity to pathogens and vaccines, yet the effects of aging on B cells are not fully known. Chronic viral infection by CMV is implicated as a driver of clonal T cell proliferations in some aging humans, but whether CMV or EBV infection contributes to alterations in the B cell repertoire with age is unclear. We have used high-throughput DNA sequencing of IGH gene rearrangements to study the BCR repertoires over two successive years in 27 individuals ranging in age from 20 to 89 y. Some features of the B cell repertoire remain stable with age, but elderly subjects show increased numbers of B cells with long CDR3 regions, a trend toward accumulation of more highly mutated IgM and IgG Ig genes, and persistent clonal B cell populations in the blood. Seropositivity for CMV or EBV infection alters B cell repertoires, regardless of the individual's age: EBV infection correlates with the presence of persistent clonal B cell expansions, whereas CMV infection correlates with the proportion of highly mutated Ab genes. These findings isolate effects of aging from those of chronic viral infection on B cell repertoires and provide a baseline for understanding human B cell responses to vaccination or infectious stimuli.
老年人对病原体和疫苗的体液免疫能力下降，但衰老对 B 细胞的影响尚不完全清楚。巨细胞病毒（CMV）的慢性病毒感染被认为是一些老年人中克隆性 T 细胞增殖的驱动因素，但 CMV 或 EBV 感染是否导致 B 细胞库随年龄而改变尚不清楚。我们使用IGH 基因重排的高通量 DNA 测序，在 27 名年龄在 20 至 89 岁的个体中连续两年研究了 BCR 库。随着年龄的增长，一些 B 细胞库的特征仍然保持稳定，但老年受试者的长 CDR3 区 B 细胞数量增加，IgM 和 IgG Ig 基因的高度突变趋势增加，以及血液中持续存在的克隆性 B 细胞群体。CMV 或 EBV 感染的血清阳性状态改变了 B 细胞库，无论个体的年龄如何：EBV 感染与持续存在的克隆性 B 细胞扩增有关，而 CMV 感染与高度突变的 Ab 基因比例有关。这些发现将衰老对 B 细胞库的影响与慢性病毒感染的影响分开，并为了解人类 B 细胞对疫苗接种或感染性刺激的反应提供了基线。
