Differential transcriptome and development of human peripheral plasma cell subsets

• Type of Material: Article
• Authors: Swertha Garimilla, Emory University; Doan Nguyen, Emory University; Jessica L. Halliley, Finger Lakes Community College; Christopher Tipton, Emory University; Alexader F. Rosenberg, University of Alabama Birmingham; Christopher F. Fucile, University of Alabama Birmingham; Celia L. Saney, Emory University; Shuya Kyu, Emory University; Denise Kaminski, University of Rochester; Yu Dian, J. Craig Venter Institute; Richard H. Scheuermann, J. Craig Venter Institute; Greg Gibson, Emory University; Inaki Sanz, Emory University; Frances Eun-Hyung Lee, Emory University
• Language: English
• Date: 2019-05-02
• Publisher: The American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2019 American Society for Clinical Investigation
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.126732
• Title of Journal or Parent Work: JCI insight
• Volume: 4
• Issue: 9
• Grant/Funding Information: This work was supported by NIH/NIAID R01AI121252, K23 AI67501, P01AI125180, U19AI1109962, 5 P01 A1078907-04, R37AI049660, U01AI045969; Autoimmunity Center of Excellence ARRA:AI056390-06S2, HHSN266200500030C (N01-AI50029), AI078907, AI049600; and NIH/NCATS UL1 TR000454.
• Keywords: IDENTIFICATION; Research & Experimental Medicine; B-CELLS; SURVIVAL; Medicine, Research & Experimental; EXPRESSION; POPULATION; HUMAN BLOOD; BONE-MARROW; RESPONSIVENESS; GENERATION; Science & Technology; Life Sciences & Biomedicine; ANTIBODY-SECRETING CELLS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

Human antibody-secreting cells (ASCs) triggered by immunization are globally recognized as CD19loCD38hiCD27hi. Yet, different vaccines give rise to antibody responses of different longevity, suggesting ASC populations are heterogeneous. We define circulating-ASC heterogeneity in vaccine responses using multicolor flow cytometry, morphology, VH repertoire, and RNA transcriptome analysis. We also tested differential survival using a human cell-free system that mimics the bone marrow (BM) microniche. In peripheral blood, we identified 3 CD19+ and 2 CD19- ASC subsets. All subsets contributed to the vaccine-specific responses and were characterized by in vivo proliferation and activation. The VH repertoire demonstrated strong oligoclonality with extensive interconnectivity among the 5 subsets and switched memory B cells. Transcriptome analysis showed separation of CD19+ and CD19- subsets that included pathways such as cell cycle, hypoxia, TNF-α, and unfolded protein response. They also demonstrated similar long-term in vitro survival after 48 days. In summary, vaccine-induced ASCs with different surface markers (CD19 and CD138) are derived from shared proliferative precursors yet express distinctive transcriptomes. Equal survival indicates that all ASC compartments are endowed with long-lived potential. Accordingly, in vivo survival of peripheral long-lived plasma cells may be determined in part by their homing and residence in the BM microniche.