Ma Lina, Tao Xinxin, He Xiaoyan, Wang Peng, Ma Long, Shi Bin, Yao Xinsheng
Department of Immunology, Center of ImmunoMolecular Engineering, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi City, 563000, China.
Immun Ageing. 2021 Apr 12;18(1):17. doi: 10.1186/s12979-021-00231-2.
The number of central and peripheral B cells and their responsiveness are decreased in aged mice. The diversity of mice central and peripheral B cell repertoires with increasing age has not been elucidated. In this study, we demonstrated that there were significant differences in the usage of some V, D, and J genes in the BCR H-CDR3 repertoire of bone marrow B cells, spleen B cells and spleen memory B cells in 3-, 12-, and 20-month-old mice. In the productive, pseudogene, and out-of-frame sequences, bone marrow B cells had significant differences in 5'J trimming with age; peripheral spleen B cells and memory B cells had significant differences in N1 insertion, N2 insertion, P5'D insertion, and 5'D trimming with age. The BCR H-CDR3 repertoire diversity of mice bone marrow B cells, spleen B cells and spleen memory B cells decreased with increasing age. The proportion of overlap in bone marrow and spleen B cells, but not spleen memory B cells, of mice at different ages was lower at 3 months than at 12 and 20 months. This study is the first to report the homogeneity and heterogeneity of the CDR3 repertoire of central and peripheral B cells change as mice age, to further investigation of the decline and response of B cell immunity in young/middle/old-aged mice.
衰老小鼠的中枢和外周B细胞数量及其反应性均降低。随着年龄增长,小鼠中枢和外周B细胞库的多样性尚未阐明。在本研究中,我们证明3月龄、12月龄和20月龄小鼠的骨髓B细胞、脾脏B细胞和脾脏记忆B细胞的BCR H-CDR3库中某些V、D和J基因的使用存在显著差异。在有功能的、假基因的和框外序列中,骨髓B细胞在5'J修剪方面随年龄有显著差异;外周脾脏B细胞和记忆B细胞在N1插入、N2插入、P5'D插入和5'D修剪方面随年龄有显著差异。小鼠骨髓B细胞、脾脏B细胞和脾脏记忆B细胞的BCR H-CDR3库多样性随年龄增长而降低。不同年龄小鼠的骨髓和脾脏B细胞(而非脾脏记忆B细胞)的重叠比例在3个月时低于12个月和20个月时。本研究首次报道了随着小鼠年龄增长,中枢和外周B细胞CDR3库的同质性和异质性变化,为进一步研究青年/中年/老年小鼠B细胞免疫的衰退和反应提供了依据。