Immunity
Volume 43, Issue 1, 21 July 2015, Pages 132-145
Journal home page for Immunity

Article
Long-Lived Plasma Cells Are Contained within the CD19CD38hiCD138+ Subset in Human Bone Marrow

https://doi.org/10.1016/j.immuni.2015.06.016Get rights and content
Under an Elsevier user license
open archive

Highlights

  • The CD19CD38hiCD138+ BM PC subset represents human LLPCs

  • CD19CD38hiCD138+ BM LLPCs are responsible for long-lived viral antibodies in serum

  • BM LLPCs have a VH repertoire that is uncoupled from other BM PC subsets

  • BM LLPCs have a unique RNA transcriptome compared to other BM PC subsets

Summary

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 CD19CD38hiCD138+ 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 more than 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19CD38hiCD138+ PCs in the BM. Finally, we found that CD19CD38hiCD138+ PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and probably 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.

Keywords

human
long-lived plasma cells
antibody secreting cells
plasmablasts
plasma cells
measles
mumps infection
vaccine
heterogeneity
bone marrow
next generation sequencing
proteomics

Cited by (0)

15

Present address: Global Biotherapeutic Technologies, Pfizer, Cambridge, MA 02139, USA

16

Co-senior author