Transcriptional and clonal characterization of B cell plasmablast diversity following primary and secondary natural DENV infection
Autor: | Damon Ellison, Stefan Fernandez, Michael K. McCracken, Tao Li, Kaitlin Victor, Richard G. Jarman, Ariadna Grinyo i Escuer, Mallorie E. Fouch, Gregory D. Gromowski, Methee Gomootsukavadee, Anuja Mathew, Benjamin J. Doranz, Alan L. Rothman, Stephen J. Thomas, Edgar Davidson, Benjamin Gabriel, Caitlin Kuklis, Jeffrey R. Currier, Hayden Siegfried, Wiriya Rutvisuttinunt, Heather Friberg, Jenny Liang, Timothy P. Endy, Adam T. Waickman, Anon Srikiatkhachorn |
---|---|
Rok vydání: | 2020 |
Předmět: |
Monoclonal antibody
0301 basic medicine medicine.medical_specialty Research paper medicine.drug_class viruses Cell Immunoglobulins lcsh:Medicine Biology Plasmablast General Biochemistry Genetics and Molecular Biology Dengue fever Dengue Single-cell RNA sequencing 03 medical and health sciences 0302 clinical medicine Medical microbiology medicine Humans RNA-Seq Cells Cultured B cell B-Lymphocytes lcsh:R5-920 lcsh:R virus diseases RNA General Medicine Dengue Virus biochemical phenomena metabolism and nutrition medicine.disease Virology Immunity Humoral 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Antibody Formation Humoral immunity Commentary biology.protein Single-Cell Analysis Antibody Transcriptome lcsh:Medicine (General) IgA |
Zdroj: | EBioMedicine, Vol 54, Iss, Pp-(2020) EBioMedicine |
ISSN: | 2352-3964 |
Popis: | Antibody-mediated humoral immunity is thought to play a central role in mediating the immunopathogenesis of acute DENV infection, but limited data are available on the diversity, specificity, and functionality of the antibody response at the molecular level elicited by primary or secondary DENV infection. In order to close this functional gap in our understanding of DENV-specific humoral immunity, we utilized high-throughput single cell RNA sequencing to investigate B cells circulating in both primary and secondary natural DENV infections. We captured full-length paired immunoglobulin receptor sequence data from 9,027 B cells from a total of 6 subjects, including 2,717 plasmablasts. In addition to IgG and IgM class-switched cells, we unexpectedly found a high proportion of the DENV-elicited plasmablasts expressing IgA, principally in individuals with primary DENV infections. These IgA class-switched cells were extensively hypermutated even in individuals with a serologically confirmed primary DENV infection. Utilizing a combination of conventional biochemical assays and high-throughput shotgun mutagenesis, we determined that DENV-reactive IgA class-switched antibodies represent a significant fraction of DENV-reactive Igs generated in response to DENV infection, and that they exhibit a comparable epitope specificity to DENV-reactive IgG antibodies. These results provide insight into the molecular-level diversity of DENV-elicited humoral immunity and identify a heretofore unappreciated IgA plasmablast response to DENV infection. Keywords: Dengue, Plasmablast, Single-cell RNA sequencing, IgA, Monoclonal antibody |
Databáze: | OpenAIRE |
Externí odkaz: |