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

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