Frontiers in Immunology (Dec 2020)

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

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

DOI
https://doi.org/10.3389/fimmu.2020.606338
Journal volume & issue
Vol. 11

Abstract

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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.

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