| Literature DB >> 26187412 |
Jessica L Halliley1, Christopher M Tipton2, Jane Liesveld3, Alexander F Rosenberg4, Jaime Darce5, Ivan V Gregoretti5, Lana Popova5, Denise Kaminiski4, Christopher F Fucile4, Igor Albizua6, Shuya Kyu6, Kuang-Yueh Chiang7, Kyle T Bradley8, Richard Burack9, Mark Slifka10, Erika Hammarlund10, Hao Wu11, Liping Zhao11, Edward E Walsh12, Ann R Falsey12, Troy D Randall13, Wan Cheung Cheung5, Iñaki Sanz2, F Eun-Hyung Lee14.
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.Entities:
Keywords: antibody secreting cells; bone marrow; heterogeneity; human; long-lived plasma cells; measles; mumps infection; next generation sequencing; plasma cells; plasmablasts; proteomics; vaccine
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Year: 2015 PMID： 26187412 PMCID： PMC4680845 DOI： 10.1016/j.immuni.2015.06.016
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745