LAUSR

The pathogenesis of systemic sclerosis (SSc) is incompletely understood but several lines of evidence suggest that B cells are involved. Effector B (Beff) cells are hyperactivated and produce autoantibodies (autoAbs) and regulatory B cells (Bregs) are decreased, whereas a recent study reported a defect in central B cell tolerance. AutoAbs appear before fibrosis and some have direct profibrotic effects, while others also induce microvasculopathy. Recently, a study found that B cells reactive to DNA-topoisomerase I (Topo I) with high affinity produce IL-6 and cause fibrosis in mice, whereas low affinity for topo I B cells produce IL-10 and inhibit fibrosis. Ibrutinib, a Bruton's tyrosine kinase inhibitor, promoted B cells with low affinity for Topo I and decreased fibrosis. These findings provide a rationale for innovative B-cell-directed strategies, such as ibrutinib or chimeric antigen receptor T cells, particularly in the early inflammatory stage of the disease.