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

• DOI: 10.1038/s41467-018-05853-7
• Publication Date: 2018-09-06T10:12:43Z
• Authors: 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; F. Eun-Hyung Lee
• Keywords: Adult; Male; 0301 basic medicine; Cell Survival; Science; Q; Tumor Necrosis Factor Ligand Superfamily Member 13; Mesenchymal Stem Cells; Middle Aged; Article; Fibronectins; 3. Good health; Young Adult; 03 medical and health sciences; 14-3-3 Proteins; Bone Marrow; Humans; Female; Antibody-Producing Cells; Cells, Cultured; Protein Binding

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 BM microenvironment required sustain long-lived plasma (LLPC) remain elusive. Here, we identify factors that maintain human ASC > 50 days vitro. The critical components cell-free vitro mimic consist products from primary mesenchymal stromal (MSC), a proliferation-inducing ligand (APRIL), and hypoxic conditions. Comparative analysis protein–protein interactions between BM-MSC proteomics with differential RNA transcriptomics LLPC two major survival factors, fibronectin YWHAZ. MSC secretome proteins conditions play role utilizing mechanisms downregulate mTORC1 signaling upregulate hypoxia signatures. In summary, niche for maturation LLPC.