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

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.606338

DOI=10.3389/fimmu.2020.606338

ISSN=1664-3224

ABSTRACT=<p>Double negative (DN) (CD19<sup>+</sup>CD20<sup>low</sup>CD27<sup>-</sup>IgD<sup>-</sup>) 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.</p>