Specific induction of double negative B cells during protective and pathogenic immune responses

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. We were able to induce DN B cells in healthy subjects following vaccination against tick borne encephalitis virus. B-cell repertoire 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.