GSE193642
ATAC-seq analysis of human blood and bone marrow antibody-secreting cell subsets
Antibody-secreting cells (ASC) circulate after vaccination and infection and migrate to the bone marrow (BM) where a subset known as long-lived plasma cells (LLPC) persist and secrete antibodies for a lifetime. The mechanisms of how circulating ASC become LLPC is not well elucidated. Here, we show that human early-minted blood ASCs have distinct morphology, transcriptomes, and epigenetics compared to human BM LLPC. Compared to blood ASC, BM LLPC have decreased nucleus/cytoplasm ratio but increased endoplasmic reticulum and numbers of mitochondria. Additionally, LLPC acquire transcriptional and epigenetic differences in multiple cellular pathways that include apoptosis. Upregulation of the anti-apoptotic genes MCL1, BCL2, BCL-XL while simultaneously downregulation of pro-apoptotic genes HRK1, CASP3, and CASP8 occurs in LLPC. Consistent with the decrease in gene expression, pro-apoptotic gene loci are less accessible in LLPC. In contrast, anti-apoptotic gene expression is increased but is not always accompanied by changes in accessibility. Importantly, we show that early-minted blood ASCs undergo morphological and transcriptional changes that make these cells resemble ex vivo BM ASCs, suggesting that the BM microniche at least in part promotes LLPC maturation. Overall, our study demonstrates that early-minted blood ASC in the BM microniche must undergo morphological, transcriptional, and epigenetic changes to mature into apoptotic-resistant LLPC. Overall design: Comparison of human blood and BM ASC accessible chromatin landscape.