Long-Lived Plasma Cells Are Contained within the CD19−CD38hiCD138+ Subset in Human Bone Marrow

• Published in: Immunity (Cambridge, Mass.) Vol. 43; no. 1; pp. 132 - 145
• Main Authors: Halliley, Jessica L., Tipton, Christopher M., Liesveld, Jane, Rosenberg, Alexander F., Darce, Jaime, Gregoretti, Ivan V., Popova, Lana, Kaminiski, Denise, Fucile, Christopher F., Albizua, Igor, Kyu, Shuya, Chiang, Kuang-Yueh, Bradley, Kyle T., Burack, Richard, Slifka, Mark, Hammarlund, Erika, Wu, Hao, Zhao, Liping, Walsh, Edward E., Falsey, Ann R., Randall, Troy D., Cheung, Wan Cheung, Sanz, Iñaki, Lee, F. Eun-Hyung
• Format: Journal Article
• Language: English
• Published: Cambridge Elsevier Inc 01.07.2015; Elsevier Limited
• Subjects: antibody secreting cells; Antigens; Bone marrow; Flow cytometry; heterogeneity; human; Immunoglobulins; Infections; long-lived plasma cells; Measles; Morphology; Mumps; mumps infection; next generation sequencing; Plasma; plasma cells; plasmablasts; Proteomics; vaccine; Vaccines; Viruses; plasmablasts; vaccine; proteomics; long-lived plasma cells; next generation sequencing; antibody secreting cells; plasma cells; mumps infection; human; measles; heterogeneity; bone marrow
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2015.06.016

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 more than 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 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. [Display omitted] •The CD19−CD38hiCD138+ BM PC subset represents human LLPCs•CD19−CD38hiCD138+ 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 Anti-viral antibodies can persist in the serum for a lifetime, but their cellular origin has remained elusive. Lee and colleagues show that long-lived plasma cells (LLPCs) in human bone marrow are contained within a CD19−CD38hiCD138+ cell population, which has an uncoupled VH repertoire representing a historical record of antigenic exposure.