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

by Wu, Ronghu , Gibson, Greg , Galipeau, Jacques , Lee, F Eun-Hyung , Albizua, Igor , Randall, Troy D , Nguyen, Doan C , Roberson, James , Lund, Frances E , Xiao, Haopeng , Sanz, Iñaki , Chiang, Kuang-Yueh , Garimalla, Swetha , Kyu, Shuya , Waller, Edmund K

in 14-3-3 Proteins - metabolism / Adult / Antibody-Producing Cells - cytology / Antibody-Producing Cells - metabolism / APRIL protein / Blood plasma / Bone marrow / Bone Marrow - metabolism / Cell proliferation / Cell survival / Cell Survival - genetics / Cell Survival - physiology / Cells, Cultured / Comparative analysis / Critical components / Female / Fibronectin / Fibronectins - metabolism / Humans / Hypoxia / Male / Mesenchymal Stem Cells - cytology / Mesenchymal Stem Cells - metabolism / Mesenchyme / Middle Aged / Peripheral blood / Plasma cells / Protein Binding / Protein interaction / Proteins / Proteomics / Ribonucleic acid / RNA / Secretome / Stromal cells / Survival / Tumor Necrosis Factor Ligand Superfamily Member 13 - metabolism / Vaccination / Young Adult

2018

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2018

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

2018

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Journal Article

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

Wu, Ronghu,

Gibson, Greg,

Galipeau, Jacques,

Lee, F Eun-Hyung,

Albizua, Igor,

Randall, Troy D,

Nguyen, Doan C,

Roberson, James,

Lund, Frances E,

Xiao, Haopeng,

Sanz, Iñaki,

Chiang, Kuang-Yueh,

Garimalla, Swetha,

Kyu, Shuya,

Waller, Edmund K

2018

Overview

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.

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Publisher

Nature Publishing Group,Nature Publishing Group UK,Nature Portfolio

Subject

14-3-3 Proteins - metabolism

/ Adult

/ Antibody-Producing Cells - cytology

/ Antibody-Producing Cells - metabolism

/ APRIL protein

/ Blood plasma

/ Bone marrow