IgG 3 + B cells are associated with the development of multiple sclerosis

• Published in: Clinical & translational immunology 2020-01, Vol.9 (5), p.e01133
• Main Authors: Marsh-Wakefield, Felix, Ashhurst, Thomas, Trend, Stephanie, McGuire, Helen M, Juillard, Pierre, Zinger, Anna, Jones, Anderson P, Kermode, Allan G, Hawke, Simon, Grau, Georges E, Hart, Prue H, Byrne, Scott N
• Format: Article
• Language: English
• Subjects: CD20 antigen; CD27 antigen; CD38 antigen; Central nervous system; Cytometry; Defects; Experiments; Immunoglobulin D; Immunoglobulin G; Light therapy; Lymphocytes B; Multiple sclerosis; Peripheral blood; Regression analysis
• ISSN: 2050-0068; 2050-0068
• DOI: 10.1002/cti2.1133

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. 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. Nine distinct CD20 IgD IgG B-cell subsets were identified. Significant changes in the proportion of CD21 CD24 CD27 CD38 and CD27 CD38 CD71 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 CD21 CD24 CD27 CD38 subset was elevated in patients with active MS, whilst narrowband UVB significantly reduced the proportion of this switched-memory B-cell subset. 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.