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

Language
en
Document Type
Article
Issue Date
2021-01-04
First published
2020-12-18
Issue Year
2020
Authors
Ruschil, Christoph
Gabernet, Gisela
Lepennetier, Gildas
Heumos, Simon
Kaminski, Miriam
Hracsko, Zsuzsanna
Irmler, Martin
Beckers, Johannes
Ziemann, Ulf
Nahnsen, Sven
Editor
Publisher
Frontiers Media S.A.
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.

Journal Title
Frontiers in Immunology
Volume
11
Citation
Frontiers in Immunology 11 (2020). <https://www.frontiersin.org/articles/10.3389/fimmu.2020.606338/full>
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