TOP1 and systemic sclerosis: In in vivo models of mice with Topoisomerase I(Top-I)–induced SSc, production of IL-10 by Top-I specific B cells in cultures with T cells and Top-I protein was significantly higher than that by conventional B cells, this effect could be overcome by injection with recombinant chimeric PD-1-Fc and PD-L2-Fc (68), thereby supporting activation of the PD-1 pathway.