Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses

Christoph Ruschil, Gisela Gabernet, Gildas Lepennetier, Simon Heumos, Miriam Kaminski, Zsuzsanna Hracsko, Martin Irmler, Johannes Beckers, Ulf Ziemann, Sven Nahnsen, Gregory P. Owens, Jeffrey L. Bennett, Bernhard Hemmer, Markus C. Kowarik

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Double negative (DN) (CD19+CD20lowCD27-IgD-) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barré syndrome, neuromyelitis optica spectrum disorder, meningitis/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with naïve B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway.

Original languageEnglish
Article number606338
JournalFrontiers in Immunology
Volume11
DOIs
StatePublished - 18 Dec 2020

Keywords

  • B cells
  • TBE vaccination
  • autoimmune disorders
  • double negative B cells
  • influenza vaccination
  • neuromyelitis optica spectrum disorder
  • vaccination

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