Age-related changes in the BACH2 and PRDM1 genes in lymphocytes from healthy donors and chronic lymphocytic leukemia patients

Abstract

BackgroundAge-related genetic changes in lymphocyte subsets are not currently well documented. BACH2 is a transcription factor that plays an important role in immune-mediated homeostasis by tightly regulating PRDM1 expression in both B-cells and T-cells. BACH2 gene expression is highly sensitive to DNA damage in aged mice. This concept led us to investigate the variation in BACH2 and also PRDM1 expression in major lymphocyte subsets with age.MethodsLymphocyte subsets from 60 healthy donors, aged from 20 to 90 years, and 41 untreated chronic lymphocytic leukemia patients were studied. BACH2 and PRDM1 gene expression was analyzed by real-time quantitative PCR. BACH2 gene expression was correlated with its protein expression. Lymphocyte apoptosis was evaluated after intracellular oxidative stress-inducing etoposide treatment of T and B cells.ResultsOur analysis shows BACH2 mRNA downregulation with age in healthy donor CD4+, CD8+ T-cells and CD19+ B-cells. Decreased BACH2 expression was also correlated with an age-related reduction in CD8 + CD28+ T-cells. We found a strong correlation between age-related BACH2 downregulation and decreased CD4+ T-cell and CD19+ B-cell apoptosis. PRDM1, as expected, was significantly upregulated in CD4+ T-cells, CD8+ T-cells and CD19+ B-cells, and inversely correlated with BACH2. A comparison of untreated chronic lymphocytic leukemia patients with age-matched healthy donors reveals that BACH2 mRNA expression was further reduced in CD4+ T-cells, CD8+ T-cells and leukemic-B cells. PRDM1 gene expression was consequently significantly upregulated in CD4+ and CD8+ T-cells in chronic lymphocytic leukemia patients but not in their leukemic B-cells.ConclusionOverall, our data suggest that BACH2 and PRDM1 genes are significantly correlated with age in human immune cells and may be involved in immunosenescence.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5276-2) contains supplementary material, which is available to authorized users.

Transcriptomic analysis of mRNAs in human whole blood identified age-specific changes in healthy individuals

“…[29] Moreover, Bach2 has been reported to affect immunosenescence since its expression was negatively associated with age in human immune cells. [30] Our study also suggested that Bach2 mRNA was decreased in elders with the highest AUC value, which supports the previous results.…”

Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC

“…PRDM1 and REST were reported to be functionally associated with aging. For instance, PRDM1 in the brown module from Asian (Chinese) was found to be significantly correlated with age in human immune cells and might be involved in immunosenescence ( Chi et al, 2019 ). REST had been reported regulated the human brain aging ( Lu et al, 2014 ).…”

Super‐killer CTLs are generated by single gene deletion of Bach2

“…Recent studies have characterized the role of BACH2 in a number of immune cell types [ 19 , 20 , 21 , 22 , 23 , 24 ]. However, changes in CTL killing have not been examined.…”