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

Ruschil, C.; Gabernet, G.; Lepennetier, G.; Heumos, S.; Kaminski, M.; Hrasko, Z.; Irmler, M.; Beckers, J.; Ziemann, U.; Nahnsen, S.; Owens, G. P.; Bennett, J. L.; Hemmer, B.; Kowarik, M. C.

doi:10.1101/2020.09.08.285148

bioRxiv · 10.1101/2020.09.08.285148

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

Ruschil, C.·Gabernet, G.·Lepennetier, G.·Heumos, S.·Kaminski, M.·Hrasko, Z.·Irmler, M.·Beckers, J.·Ziemann, U.·Nahnsen, S.·Owens, G. P.·Bennett, J. L.·Hemmer, B.·Kowarik, M. C.

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Abstract

1Double 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-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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Ruschil, C., Gabernet, G., Lepennetier, G., Heumos, S., Kaminski, M., Hrasko, Z., Irmler, M., Beckers, J., Ziemann, U., Nahnsen, S., Owens, G. P., Bennett, J. L., Hemmer, B., Kowarik, M. C.. 2020-09-11. Specific induction of double negative B cells during protective and pathogenic immune responses. https://doi.org/10.1101/2020.09.08.285148

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