Differential transcriptome and development of human peripheral plasma cell subsets

• DOI: 10.1172/jci.insight.126732
• Publication Date: 2019-04-02T16:07:51Z
• Authors: Swetha Garimilla; Doan C. Nguyen; Jessica L. Halliley; Christopher Tipton; Alexander F. Rose...; Christopher F. Fu...; Celia L. Saney; Shuya Kyu; Denise Kaminski; Yu Qian; Richard H. Scheue...; Greg Gibson; Iñaki Sanz; F. Eun-Hyung Lee
• Keywords: Adult; Male; B-Lymphocytes; Tetanus; Antigens, CD19; Plasma Cells; Vaccination; Bone Marrow Cells; Middle Aged; 3. Good health; Kinetics; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Bone Marrow; Immunoglobulin G; Antibody Formation; Humans; Female; Immunization; Antibody-Producing Cells; Transcriptome; Aged

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