Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow

• Type of Material: Article
• Authors: Jessica L. Halliley, Emory University; Christopher Tipton, Emory University; Jane Liesveld, University of Rochester; Alexander F. Rosenberg, University of Rochester; Jaime Darce, Cell Signaling Technol Inc; Ivan V. Gregoretti, Cell Signaling Technol Inc; Lana Popova, Cell Signaling Technol Inc; Denise Kaminiski, University of Rochester; Christopher F. Fucile, University of Rochester; Igor Albizua-Santin, Emory University; Shuya Kyu, Emory University; Kuang-Yueh Chiang, Emory University; Kyle Bradley, Emory University; Richard Burack, University of Rochester; Mark Slifka, Oregon Health & Sciences University; Erika Hammarlund, Oregon Health & Sciences University; Hao Wu, Emory University; Liping Zhao, Emory University; Edward E. Walsh, Rochester General Hospital; Ann R. Falsey, Rochester General Hospital; Troy D. Randall, University of Alabama at Birmingham; Wan Cheung Cheung, University of Rochester Medical Center; Ignacio Sanz, Emory University; Frances Lee, Emory University
• Language: English
• Date: 2015-07-14
• Publisher: Elsevier (Cell Press)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.immuni.2015.06.016
• Title of Journal or Parent Work: Immunity
• ISSN: 1074-7613
• Volume: 43
• Issue: 1
• Start Page: 132
• End Page: 145
• Grant/Funding Information: NIH: K23 AI67501, R21AI109601, R21AI094218, P01 A1078907, R37AI049660, U01AI045969, Autoimmunity Center of Excellence- ARRA:AI056390-06S2, HHSN266200500030C (N01-AI50029), AI078907, AI049600, NIH/NCATS UL1 TR000454, UO1 AI082196, Oregon National Primate Research Center grant, 8P51 OD011092-53, R01 AI097357, and U19 AI109962.
• Keywords: HUMAN MONOCLONAL-ANTIBODIES; SURVIVAL; BLOOD; SECRETING CELLS; Immunology; EXPRESSION; MEMORY B-CELLS; RESPONSIVENESS; Science & Technology; CLONING; Life Sciences & Biomedicine; DIFFERENTIATION; HUMORAL IMMUNITY
• Research Categories: Health Sciences, Pathology; Biology, Molecular; Health Sciences, Immunology

Abstract

Antibody responses to viral infections are sustained for decades by long-lived plasma cells (LLPCs). However, LLPCs have yet to be characterized in humans. Here we used CD19, CD38, and CD138 to identify four PC subsets in human bone marrow (BM). We found that the CD19−CD38hiCD138+ subset was morphologically distinct, differentially expressed PC-associated genes and exclusively contained PCs specific for viral antigens to which the subjects had not been exposed for over 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19−CD38hiCD138+ PCs in the BM. Finally, we found that CD19−CD38hiCD138+ PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and likely represents the B cell response’s “historical record” of antigenic exposure. Thus, our studies define human LLPCs and provide a mechanism for the life-long maintenance of anti-viral antibodies in the serum.