Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow
Jessica L Halliley, Christopher M Tipton, Jane Liesveld, Alexander F Rosenberg, Jaime Darce, Ivan V Gregoretti, Lana Popova, Denise Kaminiski, Christopher F Fucile, Igor Albizua, Shuya Kyu, Kuang-Yueh Chiang, Kyle T Bradley, Richard Burack, Mark Slifka, Erika Hammarlund, Hao Wu, Liping Zhao, Edward E Walsh, Ann R Falsey, Troy D Randall, Wan Cheung Cheung, Iñaki Sanz, F Eun-Hyung Lee, Jessica L Halliley, Christopher M Tipton, Jane Liesveld, Alexander F Rosenberg, Jaime Darce, Ivan V Gregoretti, Lana Popova, Denise Kaminiski, Christopher F Fucile, Igor Albizua, Shuya Kyu, Kuang-Yueh Chiang, Kyle T Bradley, Richard Burack, Mark Slifka, Erika Hammarlund, Hao Wu, Liping Zhao, Edward E Walsh, Ann R Falsey, Troy D Randall, Wan Cheung Cheung, Iñaki Sanz, F Eun-Hyung Lee
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(-)CD38(hi)CD138(+) 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 CD19(-)CD38(hi)CD138(+) PCs in the BM. Finally, we found that CD19(-)CD38(hi)CD138(+) 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: antibody secreting cells; bone marrow; heterogeneity; human; long-lived plasma cells; measles; mumps infection; next generation sequencing; plasma cells; plasmablasts; proteomics; vaccine.
Conflict of interest statement
Conflicts of Interests: 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.
Copyright © 2015 Elsevier Inc. All rights reserved.
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Source: PubMed