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Temporal Stability and Molecular Persistence of the Bone Marrow Plasma Cell Antibody Repertoire

Gabriel C. Wu, Nai-Kong V. Cheung, George Georgiou, Edward M. Marcotte, Gregory C. Ippolito
doi: https://doi.org/10.1101/066878
Gabriel C. Wu
1Center for Systems and Synthetic Biology University of Texas at Austin, Austin, TX, USA
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Nai-Kong V. Cheung
3Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
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George Georgiou
2Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA
4Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA
5Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA
6Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX, USA
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Edward M. Marcotte
1Center for Systems and Synthetic Biology University of Texas at Austin, Austin, TX, USA
2Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA
6Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX, USA
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  • For correspondence: marcotte@icmb.utexas.edu gci@mail.utexas.edu
Gregory C. Ippolito
2Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA
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  • For correspondence: marcotte@icmb.utexas.edu gci@mail.utexas.edu
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ABSTRACT

Plasma cells in human bone marrow (BM PCs) are thought to be intrinsically long-lived and to be responsible for sustaining lifelong immunity through the constitutive secretion of antibody—but the underlying basis for this serological memory remains controversial. Here, we analyzed the molecular persistence of serological immunity by an examination of BM PC immunoglobulin heavy-chain (IGH) transcripts derived from serial bone marrow specimens obtained during a span of several years. Using high-throughput sequence analysis of the same individual for 6.5 years, we show that the BM PC repertoire is remarkably stable over time. We find that the bias in IGH V, D, and J individual gene usage and also the combinatorial V–D, V–J, D–J, and V-D-J usage across time to be nearly static. When compared to a second donor with time points 2 years apart, these overall patterns are preserved, and surprisingly, we find high correlation of gene usage between the two donors. Lastly, we report the persistence of numerous BM PC clonal clusters (~2%) identifiable across 6.5 years at all time points assayed, supporting a model of serological memory based, at least in part, upon intrinsic longevity of human PCs. We anticipate that this longitudinal study will facilitate the ability to differentiate between healthy and diseased antibody repertoire states, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.

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Posted August 02, 2016.
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Temporal Stability and Molecular Persistence of the Bone Marrow Plasma Cell Antibody Repertoire
Gabriel C. Wu, Nai-Kong V. Cheung, George Georgiou, Edward M. Marcotte, Gregory C. Ippolito
bioRxiv 066878; doi: https://doi.org/10.1101/066878
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Temporal Stability and Molecular Persistence of the Bone Marrow Plasma Cell Antibody Repertoire
Gabriel C. Wu, Nai-Kong V. Cheung, George Georgiou, Edward M. Marcotte, Gregory C. Ippolito
bioRxiv 066878; doi: https://doi.org/10.1101/066878

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