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

Nat Commun. 2016 Dec 21:7:13838. doi: 10.1038/ncomms13838.

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.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Antibodies / immunology
  • Antibodies / metabolism
  • Antibody Formation / immunology*
  • Bone Marrow / immunology*
  • Bone Marrow / metabolism
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • Child
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Male
  • Neuroblastoma / genetics
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • Prospective Studies

Substances

  • Antibodies
  • Immunoglobulin Heavy Chains