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:10.1038/ncomms13838

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

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6.5 years, supporting a model of serological memory based upon intrinsic longevity of human plasma cells. Donors were adolescents who completely recovered from neuroblastoma prior to the start of this study. Our work will facilitate differentiation between healthy and diseased antibody repertoires, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.

Original language	English (US)
Article number	13838
Journal	Nature Communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13838
State	Published - Dec 21 2016

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
Physics and Astronomy(all)

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title = "Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire",

abstract = "Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6.5 years, supporting a model of serological memory based upon intrinsic longevity of human plasma cells. Donors were adolescents who completely recovered from neuroblastoma prior to the start of this study. Our work will facilitate differentiation between healthy and diseased antibody repertoires, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.",

author = "Wu, {Gabriel C.} and Cheung, {Nai Kong V.} and George Georgiou and Marcotte, {Edward M.} and Ippolito, {Gregory C.}",

note = "Funding Information: This work was supported by NSF Graduate Research Fellowship DGE-1110007 (to G.C.W.), HDTRA1-12-C-0105 from DTRA (G.G., G.C.I., E.M.M.), WHO GPEI (G.C.I.), and grants from the NIH, NSF and Welch Foundation (F-1515) to E.M.M. Publisher Copyright: {\textcopyright} The Author(s) 2016. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",

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doi = "10.1038/ncomms13838",

language = "English (US)",

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AU - Wu, Gabriel C.

AU - Cheung, Nai Kong V.

AU - Georgiou, George

AU - Marcotte, Edward M.

AU - Ippolito, Gregory C.

N1 - Funding Information: This work was supported by NSF Graduate Research Fellowship DGE-1110007 (to G.C.W.), HDTRA1-12-C-0105 from DTRA (G.G., G.C.I., E.M.M.), WHO GPEI (G.C.I.), and grants from the NIH, NSF and Welch Foundation (F-1515) to E.M.M. Publisher Copyright: © The Author(s) 2016. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.

PY - 2016/12/21

Y1 - 2016/12/21

N2 - Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6.5 years, supporting a model of serological memory based upon intrinsic longevity of human plasma cells. Donors were adolescents who completely recovered from neuroblastoma prior to the start of this study. Our work will facilitate differentiation between healthy and diseased antibody repertoires, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.

AB - Plasma cells in human bone marrow (BM) are thought to be responsible for sustaining lifelong immunity, but its underlying basis is controversial. Here we use high-throughput sequence analysis of the same individual across 6.5 years to show that the BM plasma cell immunoglobulin heavy chain repertoire is remarkably stable over time. We find a nearly static bias in individual and combinatorial gene usage across time. Analysis of a second donor corroborates these observations. We also report the persistence of numerous BM plasma cell clonotypes (∼2%) identifiable at all points assayed across 6.5 years, supporting a model of serological memory based upon intrinsic longevity of human plasma cells. Donors were adolescents who completely recovered from neuroblastoma prior to the start of this study. Our work will facilitate differentiation between healthy and diseased antibody repertoires, by serving as a point of comparison with future deep-sequencing studies involving immune intervention.

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Temporal stability and molecular persistence of the bone marrow plasma cell antibody repertoire

Abstract

ASJC Scopus subject areas

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