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• W2891470462 abstract "Abstract Human antibody-secreting cells (ASC) in peripheral blood are found after vaccination or infection but rapidly apoptose unless they migrate to the bone marrow (BM). Yet, elements of the BM microenvironment required to sustain long-lived plasma cells (LLPC) remain elusive. Here, we identify BM factors that maintain human ASC > 50 days in vitro. The critical components of the cell-free in vitro BM mimic consist of products from primary BM mesenchymal stromal cells (MSC), a proliferation-inducing ligand (APRIL), and hypoxic conditions. Comparative analysis of protein–protein interactions between BM-MSC proteomics with differential RNA transcriptomics of blood ASC and BM LLPC identify two major survival factors, fibronectin and YWHAZ. The MSC secretome proteins and hypoxic conditions play a role in LLPC survival utilizing mechanisms that downregulate mTORC1 signaling and upregulate hypoxia signatures. In summary, we identify elements of the BM survival niche critical for maturation of blood ASC to BM LLPC." @default.
• W2891470462 created "2018-09-27" @default.
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• W2891470462 date "2018-09-12" @default.
• W2891470462 modified "2023-10-14" @default.
• W2891470462 title "Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion" @default.
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• W2891470462 doi "https://doi.org/10.1038/s41467-018-05853-7" @default.
• W2891470462 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6135805" @default.
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