Since the antigen affinity of B cells varies from cell to cell, functional analysis in each B cell has been difficult from technical aspects. Especially in autoimmune diseases, promising pathogenic B cells have not been adequately studied to date because of the rarity. Here, we analyzed the single-cell function of autoantigen-reactive B cells in systemic sclerosis (SSc). Topo I-reactive B cells were extracted from peripheral blood of SSc patients. mRNA expression and protein expression analysis, co-culture analysis with T cells in micro-space, and cytokine and antigen binding capacity analysis were performed. Functional, cytokine, and antigen binding capacity analysis were also performed in the SSc murine model. We also confirmed the pathogenicity by adoptive transfer experiments. The significance of Bruton's tyrosine kinase (BTK) inhibitors in this murine model was also investigated. Topo I-reactive B cells with high affinity for topo I antigen produced large amounts of inflammatory cytokines, such as interleukin (IL)-6 and IL-23, and the frequency of those cells was high. Those with low affinity produced a large amount of the inhibitory cytokines, such as IL-10 and IL-35, and the percentage of those cells was high. The former induced T helper 17 cells and resulted in fibrosis. The latter induced regulatory T cells and suppressed fibrosis. Furthermore, the more B cells with higher antigen affinity, the more skin sclerosis and the worse lung function. Neutralization or deficiency of inflammatory cytokines, such as IL-6 or IL-23, reduced antigen affinity of topo I-reactive B cells and inhibited fibrosis. BTK inhibitor reduced topo I-reactive B cells with high affinity, increased topo I-reactive B cells with low affinity, and inhibited fibrosis. Thus, it might be that autoantigen-reactive B cells produce inflammatory cytokines or inhibitory cytokines according to their antigen affinity, which in turn affect T cells through cytokines from autoantigen reactive B cells, and contributes to fibrosis.

ESDR019 - Single cell level protein analysis of autoantigen-reactive B cells in systemic sclerosis and the murine model

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.