Factors of the bone marrow microniche that support human plasma cell survival and immunoglobulin secretion
Authors: Igor Albizua
Troy D Randall
Haopeng Xiao
Jacques Galipeau
Doan C Nguyen
Ronghu Wu
Greg Gibson
Frances E Lund
Shuya Kyu
Swetha Garimalla
Edmund K Waller
James Roberson
Kuang-Yueh Chiang
F Eun-Hyung Lee
Iñaki Sanz
Journal: Nature communications (2018)
Discipline: Multidisciplinary
Keywords: Human antibody-secreting cells; peripheral blood; bone marrow; long-lived plasma cells; BM microenvironment
Affiliations: Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University, Atlanta, GA, USA., School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA., School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA., Department of Human Genetics, Emory University, Atlanta, GA, USA., Department of Medicine & University of Wisconsin Carbone Cancer Center, University of Wisconsin in Madison, Madison, WI, USA., Division of Hematology & Oncology, University of Toronto, Toronto, ON, Canada., Pediatrics & Hematology/Oncology, Emory University, Atlanta, GA, USA., Department of Orthopedics, Emory University, Atlanta, GA, USA., Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA., Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA., Division of Rheumatology, Emory University, Atlanta, GA, USA., Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA., Division of Pulmonary, Allergy, Critical Care & Sleep Medicine, Emory University, Atlanta, GA, USA. ., Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA. .

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 &gt; 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. 

Retracted: No

PubPeer comments:
 Correction to: Nature Communications; https: doi.org 10.1038 s41467-018-05853-7; published online 12 September 2018 The original version of this Article omitted a declaration from the Competing interests statement, which should have included the following: u2018A patent has been applied for by Emory University with F.E.L., I.S., and D.C.N. as named inventors. The patent application number is PCT US2016 036650u2019. This has now been corrected in both the PDF and HTML versions of the Article. From https: www.nature.com articles s41467-019-08400-0 ,