Abstract
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.
Highlights
The percentage of B cells and antibody category conversion and reorganization decrease with age [1, 2]
Mice bone marrow B cell, spleen B cell and memory B cell CDR3 repertoire The concentration and purity of multiplex PCR products were in accordance with High-Throughput sequencing (HTS) requirements (Fig. S1)
3, 12, and 20-month-old mice were used as subjects, and HTS was used to compare and analyze the homogeneity and heterogeneity of the productive, pseudogene, and out-offrame sequences of the B Cell receptor (BCR) Heavy chain complementarity determining region 3 (H-CDR3) repertoire in bone marrow and spleen
Summary
The percentage of B cells and antibody category conversion and reorganization decrease with age [1, 2]. The increase in memory B cell clones is closely related to the immune system status of elderly individuals [4,5,6]. The diversity of the naïve BCR H-CDR3 repertoire is derived from the rearrangement of the germline V(D) J gene in the bone marrow [7] Human studies have shown that the lifespan of B cells in elderly individuals is increased, and the production in the bone marrow is reduced [10, 11]. B cell expansion clones increase with age [12, 13]. The repertoire is closely related to changes in age before and after immunization in mice [14]. How the homogeneity and heterogeneity of the CDR3 repertoire of
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