Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses.
Front Immunol. 2020 Dec 18;11:606338. doi: 10.3389/fimmu.2020.606338. PMID: 33391273; PMCID: PMC7775384.
|Authors/Editors:||Ruschil C, Gabernet G, Lepennetier G, Heumos S, Kaminski M, Hracsko Z, Irmler M, Beckers J, Ziemann U, Nahnsen S, Owens GP, Bennett JL, Hemmer B Kowarik MC.|
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.