IgG B cells are associated with the development of multiple sclerosis.

Objectives: Disease-modifying therapies (DMTs) targeting B cells are amongst the most effective for preventing multiple sclerosis (MS) progression. IgG antibodies and their uncharacterised B-cell clones are predicted to play a pathogenic role in MS. Identifying subsets of IgG B cells involved in MS progression could improve diagnosis, could inform timely disease intervention and may lead to new DMTs that target B cells more specifically.

Methods: We designed a 31-parameter B-cell-focused mass cytometry panel to interrogate the role of peripheral blood IgG B cells in MS progression of two different patient cohorts: one to investigate the B-cell subsets involved in conversion from clinically isolated syndrome (CIS) to MS; and another to compare MS patients with inactive or active stages of disease. Each independent cohort included a group of non-MS controls.

Results: Nine distinct CD20IgDIgG B-cell subsets were identified. Significant changes in the proportion of CD21CD24CD27CD38 and CD27CD38CD71 memory B-cell subsets correlated with changes in serum IgG levels and time to conversion from CIS to MS. The same CD38 double-negative B-cell subset was significantly elevated in MS patients with active forms of the disease. A third CD21CD24CD27CD38 subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switched-memory B-cell subset.

Conclusion: We have identified previously uncharacterised subsets of IgG B cells and shown them to correlate with autoimmune attacks on the central nervous system (CNS). These results highlight the potential for therapies that specifically target IgG B cells to impact MS progression.