Differential transcriptome and development of human peripheral plasma cell subsets.

Differential transcriptome and development of human peripheral plasma cell subsets.

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Authors: Garimilla S, Nguyen DC, Halliley JL, Tipton C, Rosenberg AF, Fucile CF, Saney CL, Kyu S, Kaminski D, Qian Y, Scheuermann RH, Gibson G, Sanz I, Lee FE
Title: Differential transcriptome and development of human peripheral plasma cell subsets.
Citation: JCI insight. 2019-05-02; 4.9: .
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-α, 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.
PMID: 31045577