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Immunity. 2015 Jul 21;43(1):132-45. doi: 10.1016/j.immuni.2015.06.016. Epub 2015 Jul 14.

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

Author information

1
Divisions of Pulmonary, Allergy, & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA; Pulmonary & Critical Care Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
2
Division of Rheumatology, Emory University, Atlanta, GA 30322, USA; Lowance Center for Human Immunology in the Departments of Medicine and Pediatrics, Emory University, Atlanta, GA 30322, USA.
3
Divisions of Hematology/Oncology/James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY 14642, USA.
4
Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY 14642, USA.
5
Cell Signaling Technology, Inc., Danvers, MA 01923, USA.
6
Divisions of Pulmonary, Allergy, & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA.
7
Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University, Atlanta, GA 30322, USA.
8
Department of Pathology & Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
9
Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
10
Oregon Health & Sciences University, Beaverton, OR 97006, USA.
11
Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA 30322, USA.
12
Division of Infectious Diseases, University of Rochester Medical Center & Rochester General Hospital, Rochester, NY 14621, USA.
13
Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
14
Divisions of Pulmonary, Allergy, & Critical Care Medicine, Emory University, Atlanta, GA 30322, USA; Lowance Center for Human Immunology in the Departments of Medicine and Pediatrics, Emory University, Atlanta, GA 30322, USA. Electronic address: f.e.lee@emory.edu.

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(-)CD38(hi)CD138(+) 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 more than 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19(-)CD38(hi)CD138(+) PCs in the BM. Finally, we found that CD19(-)CD38(hi)CD138(+) PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and probably 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.

KEYWORDS:

antibody secreting cells; bone marrow; heterogeneity; human; long-lived plasma cells; measles; mumps infection; next generation sequencing; plasma cells; plasmablasts; proteomics; vaccine

PMID:
26187412
PMCID:
PMC4680845
DOI:
10.1016/j.immuni.2015.06.016
[Indexed for MEDLINE]
Free PMC Article

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