Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion

Doan C. Nguyen, Swetha Garimalla, Haopeng Xiao, Shuya Kyu, Igor Albizua, Jacques Galipeau, Kuang-Yueh Chiang, Edmund K. Waller, Ronghu Wu, Greg Gibson, James Roberson, Frances E. Lund, Troy D. Randall, Iñaki Sanz and F. Eun-Hyung Lee ()
Additional contact information
Doan C. Nguyen: Emory University
Swetha Garimalla: Georgia Institute of Technology
Haopeng Xiao: Georgia Institute of Technology
Shuya Kyu: Emory University
Igor Albizua: Emory University
Jacques Galipeau: University of Wisconsin in Madison
Kuang-Yueh Chiang: University of Toronto
Edmund K. Waller: Emory University
Ronghu Wu: Georgia Institute of Technology
Greg Gibson: Georgia Institute of Technology
James Roberson: Emory University
Frances E. Lund: University of Alabama at Birmingham
Troy D. Randall: University of Alabama at Birmingham
Iñaki Sanz: Emory University
F. Eun-Hyung Lee: Emory University

Nature Communications, 2018, vol. 9, issue 1, 1-12

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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05853-7

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DOI: 10.1038/s41467-018-05853-7

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