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Differential transcriptome and development of human peripheral plasma cell subsets.

ABSTRACT: Human antibody-secreting cells (ASCs) triggered by immunization are globally recognized as CD19loCD38hiCD27hi. Yet, different vaccines give rise to antibody responses of different longevity, suggesting ASC populations are heterogeneous. We define circulating-ASC heterogeneity in vaccine responses using multicolor flow cytometry, morphology, VH repertoire, and RNA transcriptome analysis. We also tested differential survival using a human cell-free system that mimics the bone marrow (BM) microniche. In peripheral blood, we identified 3 CD19+ and 2 CD19- ASC subsets. All subsets contributed to the vaccine-specific responses and were characterized by in vivo proliferation and activation. The VH repertoire demonstrated strong oligoclonality with extensive interconnectivity among the 5 subsets and switched memory B cells. Transcriptome analysis showed separation of CD19+ and CD19- subsets that included pathways such as cell cycle, hypoxia, TNF-?, and unfolded protein response. They also demonstrated similar long-term in vitro survival after 48 days. In summary, vaccine-induced ASCs with different surface markers (CD19 and CD138) are derived from shared proliferative precursors yet express distinctive transcriptomes. Equal survival indicates that all ASC compartments are endowed with long-lived potential. Accordingly, in vivo survival of peripheral long-lived plasma cells may be determined in part by their homing and residence in the BM microniche.

SUBMITTER: Garimalla S

PROVIDER: S-EPMC6538338 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Differential transcriptome and development of human peripheral plasma cell subsets.

Garimalla Swetha S Nguyen Doan C DC Halliley Jessica L JL Tipton Christopher C Rosenberg Alexander F AF Fucile Christopher F CF Saney Celia L CL Kyu Shuya S Kaminski Denise D Qian Yu Y Scheuermann Richard H RH Gibson Greg G Sanz Iñaki I Lee F Eun-Hyung FE

JCI insight 20190502 9

Human antibody-secreting cells (ASCs) triggered by immunization are globally recognized as CD19loCD38hiCD27hi. Yet, different vaccines give rise to antibody responses of different longevity, suggesting ASC populations are heterogeneous. We define circulating-ASC heterogeneity in vaccine responses using multicolor flow cytometry, morphology, VH repertoire, and RNA transcriptome analysis. We also tested differential survival using a human cell-free system that mimics the bone marrow (BM) micronich ...[more]

PMID: 31045577

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Differential transcriptome and development of human peripheral plasma cell subsets.

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Differential transcriptome and development of human peripheral plasma cell subsets.

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