CD11c+ B cells in relapsing–remitting multiple sclerosis and effects of anti-CD20 therapy

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B cells are important in the pathogenesis of multiple sclerosis. It is yet unknown which subsets may be involved, but atypical B cells have been proposed as mediators of autoimmunity. In this study, we investigated differences in B-cell subsets between controls and patients with untreated and anti-CD20-treated multiple sclerosis.

We recruited 155 participants for an exploratory cohort comprising peripheral blood and cerebrospinal fluid, and a validation cohort comprising peripheral blood. Flow cytometry was used to characterize B-cell phenotypes and effector functions of CD11c+ atypical B cells.

There were no differences in circulating B cells between controls and untreated multiple sclerosis. As expected, anti-CD20-treated patients had a markedly lower B-cell count. Of B cells remaining after treatment, we observed higher proportions of CD11c+ B cells and plasmablasts. CD11c+ B cells were expanded in cerebrospinal fluid compared to peripheral blood in controls and untreated multiple sclerosis. Surprisingly, the proportion of CD11c+ cerebrospinal fluid B cells was higher in controls and after anti-CD20 therapy than in untreated multiple sclerosis. Apart from the presence of plasmablasts, the cerebrospinal fluid B-cell composition after anti-CD20 therapy resembled that of controls. CD11c+ B cells demonstrated a high potential for both proinflammatory and regulatory cytokine production.

The study demonstrates that CD11c+ B cells and plasmablasts are less efficiently depleted by anti-CD20 therapy, and that CD11c+ B cells comprise a phenotypically and functionally distinct, albeit heterogenous, B-cell subset with the capacity of exerting both proinflammatory and regulatory functions.
TidsskriftAnnals of Clinical and Translational Neurology
Udgave nummer4
Sider (fra-til)926-937
Antal sider12
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
We wish to thank study nurses Karina Scotland and Sidsel Walter Nielsen, laboratory technician Lisbeth Stolpe and nurses Gitte Foget, Isabel Callesen and Solveig Rosenørn for their indispensable assistance. The study and SEM were funded by the Danish Regions through the DanNORMS grant. FS holds a professorship at the Faculty of Health Sciences and Medicine, University of Copenhagen sponsored by the Danish Multiple Sclerosis Society.

Publisher Copyright:
© 2024 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

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