PMC:7417788 / 33765-36837 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7417788","sourcedb":"PMC","sourceid":"7417788","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7417788","text":"Although the antigen repertoire sensed by immunoglobulin receptors on both TCs (TCRs) and BCs (BCRs) is known to continuously evolve with age (Yuseff et al., 2013), the phenomenon of aging-associated TCR and BCR repertoire constriction has not yet been studied at the single-cell level. Here, we employed scTCR/BCR-seq to assess immune cell clonal expansion in the YA and AA groups. We found that relative to the YA group, the AA group was associated with a substantial decrease in unique clonotypes both in TCRs and BCRs (Fig. 5A and 5B), suggesting that both TCR and BCR clonality increased with age. Moreover, quantification of the most highly expanded (maximum) clone for each research subject showed that the ratios of the maximum clones were higher in the AA group than in the YA group (Fig. 5C). Although an aging-related clonal lymphocyte population may reflect an existing adaptive immunity of the elderly, the overall diversity was decreased in the AA group compared to the YA group (Fig. 5D). Analysis of TCR and BCR distributions across different TC and BC subtypes revealed that loss of repertoire diversity was pronounced in CD8+, T-mito and memory BCs of the AA group (Fig. 5E and 5F). To understand how clonally expanded TCs could be affected by aging, we performed DEG analysis of clonal cells between YA and AA groups and revealed increased expression of effector and memory TC signatures, including GZMB, GZMK, CXCR4, CCL3 and various TCR genes in the aged group (Fig. 5G; Table S12A). In addition, clonal BCs showed aging-associated changes, including increased expression of S100A family genes and decreased levels of naive signature genes such as IGHM and TCL1A in the aged BCs compared to their young counterparts (Fig. 5H; Table S 12B).\nFigure 5 Abnormal TCR and BCR repertoire during aging. (A) Pie plots showing TCR clone differences across YA and AA groups. (B) Pie plots showing BCR clone differences across YA and AA groups. (C) Percentage of maximum clones between YA (n = 8) and AA groups (n = 8). (D) Diversity of TCR and BCR between YA (n = 8) and AA groups (n = 8). (E) Diversity of TCR in T cell subsets between YA (n = 8) and AA groups (n = 8). (F) Diversity of BCR in B cell subsets between YA (n = 8) and AA groups (n = 8). (G) Volcano plot showing DEGs of clonal T cells between the YA and AA groups. P values were calculated using a paired, two-sided Wilcoxon test and FDR was corrected using the Benjamini-Hochberg procedure. (H) Volcano plot showing DEGs of clonal B cells between the YA and AA groups. P values were calculated using a paired, two-sided Wilcoxon test and FDR was corrected using the Benjamini-Hochberg procedure. (I) Chord diagram showing pairing of V and J segments within the TRB subset from the AA group. Chord widths represent the proportion of sequences with a given V (colored) and J (gray) segment pairing. (J) Chord diagram showing pairing of V and J segments within the IGH subset from the AA group. Chord widths represent the proportion of sequences with a given V (colored) and J (gray) segment 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