Its effectiveness varies from patient to patient (Mohammed et al., 2017), suggesting that the therapeutic effect may be determined by relative abundance of pathogenic B cells with high affinity for topo I. Our results also demonstrate that inhibition of affinity maturation to topo I by BTK inhibitors induced regulatory autoreactive B cells and thereby suppressed skin and lung fibrosis (Figure 7), suggesting that BTK would be a potential therapeutic target for SSc. Here, BTK is linked to systemic sclerosis.