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.
FörderungenNIHR01EY022936 German Ministry of Research and Education (BMBF) 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 DFG Helmholtz Alliance 'Aging and Metabolic Programming, AMPro' MultipleMS EU consortium German Federal Ministry for Education and Research [Munich] Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy DIFUTURE (Data Integration for Future Medicine) Munich Cluster for Systems Neurology (SyNergy) fortune/PATE from the medical faculty, Eberhard-Karls University of Tubingen