High-Resolution Temporal Response Patterns to Influenza Vaccine Reveal a Distinct Human Plasma Cell Gene Signature

• Published in: Scientific reports 2013-07, Vol.3 (1), p.2327, Article 2327
• Main Authors: Henn, Alicia D., Wu, Shuang, Qiu, Xing, Ruda, Melissa, Stover, Michael, Yang, Hongmei, Liu, Zhiping, Welle, Stephen L., Holden-Wiltse, Jeanne, Wu, Hulin, Zand, Martin S.
• Format: Article
• Language: English
• Subjects: 631/250/2152/1566/1571; 631/250/590/1883; 631/553/1833; 631/553/2701; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Blood Proteins - genetics; Blood Proteins - immunology; Cell lineage; Cells, Cultured; Dendritic cells; Gene expression; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Genes; Humanities and Social Sciences; Humans; Immunization; Influenza; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Leukocytes (mononuclear); Lymphocytes B; multidisciplinary; Peripheral blood mononuclear cells; Plasma cells; Science; Transcription; Transcriptome - drug effects; Transcriptome - immunology; Vaccination; Vaccines
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep02327

To identify sources of inter-subject variation in vaccine responses, we performed high-frequency sampling of human peripheral blood cells post-vaccination, followed by a novel systems biology analysis. Functional principal component analysis was used to examine time varying B cell vaccine responses. In subjects vaccinated within the previous three years, 90% of transcriptome variation was explained by a single subject-specific mathematical pattern. Within individual vaccine response patterns, a common subset of 742 genes was strongly correlated with migrating plasma cells. Of these, 366 genes were associated with human plasmablasts differentiating in vitro . Additionally, subject-specific temporal transcriptome patterns in peripheral blood mononuclear cells identified migration of myeloid/dendritic cell lineage cells one day after vaccination. Upstream analyses of transcriptome changes suggested both shared and subject-specific transcription groups underlying larger patterns. With robust statistical methods, time-varying response characteristics of individual subjects were effectively captured along with a shared plasma cell gene signature.