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.
authors.affiliation: Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Gabriel C
authors.initials: GC
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Nai-Kong V
authors.initials: NV
authors.lastname: Cheung
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.|Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: George
authors.initials: G
authors.lastname: Georgiou
authors.affiliation: Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas 78712, USA.|Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.|Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Marcotte
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Ippolito
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D002648:Child; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D009447:Neuroblastoma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D000906:Antibodies; D007143:Immunoglobulin Heavy Chains