期刊
FRONTIERS IN IMMUNOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.606338
关键词
influenza vaccination; TBE vaccination; vaccination; B cells; double negative B cells; neuromyelitis optica spectrum disorder; autoimmune disorders
类别
资金
- fortune/PATE from the medical faculty, Eberhard-Karls University of Tubingen [2536-0-0]
- German Ministry of Research and Education (BMBF) [01ZX1301F]
- Ministry of Science, Research and Arts of Baden-Wurttemberg (MWK) for the Science Data Centre project BioDATEN
- Central Innovation Program (ZIM) for SMEs of the Federal Ministry for Economic Affairs and Energy of Germany
- Federal Ministry of Education and Research (BMBF)
- Baden-Wurttemberg Ministry of Science as part of the Excellence Strategy of the German Federal and State Governments [Sonderforschungsbereich SFB/TR 209]
- DFG [EXC 2180 - 390900677]
- Helmholtz Alliance 'Aging and Metabolic Programming, AMPro'
- MultipleMS EU consortium
- German Federal Ministry for Education and Research [Munich] [01GI1601D]
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy [EXC 2145 SyNergy -ID 390857198]
- DIFUTURE (Data Integration for Future Medicine) [BMBF 01ZZ1804[A-I]]
- Munich Cluster for Systems Neurology (SyNergy)
- [NIHR01EY022936]
Double negative (DN) (CD19(+)CD20(low)CD27(-)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-Barre 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 naive 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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