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Author Notes:

Email: f.e.lee@emory.edu

The authors would like to thank Jennifer Scantlin, Claudine Nkurunziza, Deanna Maffett, and Julie Kozarsky for human subject recruitment.

We also appreciate Edmund Waller, Jeremy Bechelli, Karen Rosell and the Atlanta Clinical & Translational Science Institute (ACTSI) for their assistance with the bone marrow aspirates, Chelsea Cook, Flow Cytometry Core at URMC, and Wayne Harris at Emory University, and Jennifer Hom, Linda Kippner, and Melissa Kemp for assistance in preparation of the manuscript.

F.E.L. has research grants with Genentech and is the founder of MicroBplex. I.S. consults for Pfizer,Genentech, and has research grants with Biogen and Takeda Pharmaceuticals.

A.R.F. consults for AstraZeneca, Medimmune, Sanofi Pasteur, and Wyeth and has research grants from GSK and Sanofi Pasteur.

E.E.W. has research grants from GSK and Sanofi Pasteur and consults for Astra Zeneca.

J.L.H., C.T., J.L, A.F.R., J.D., I.V.G, L.P., D.K., C.F.F., I.A.S., S.K., K-Y.C., K.T.B., R.B., M.S., E.H., L.Z., T.D.R., and W.C.C. have no conflicts of interest.

Subjects:

Research Funding:

NIH: K23 AI67501, R21AI109601, R21AI094218, P01 A1078907, R37AI049660, U01AI045969, Autoimmunity Center of Excellence- ARRA:AI056390-06S2, HHSN266200500030C (N01-AI50029), AI078907, AI049600, NIH/NCATS UL1 TR000454, UO1 AI082196, Oregon National Primate Research Center grant, 8P51 OD011092-53, R01 AI097357, and U19 AI109962.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • MEMORY B-CELLS
  • HUMAN MONOCLONAL-ANTIBODIES
  • HUMORAL IMMUNITY
  • SECRETING CELLS
  • BLOOD
  • SURVIVAL
  • EXPRESSION
  • CLONING
  • DIFFERENTIATION
  • RESPONSIVENESS

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

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Journal Title:

Immunity

Volume:

Volume 43, Number 1

Publisher:

, Pages 132-145

Type of Work:

Article | Post-print: After Peer Review

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−CD38hiCD138+ 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 over 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19−CD38hiCD138+ PCs in the BM. Finally, we found that CD19−CD38hiCD138+ PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and likely 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.

Copyright information:

© 2015 Elsevier Inc.

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