Effect of Brd4 inhibition on the percentages of naïve, memory, plasmablast, and plasma cells in CD19+ B cells from patients with SLE
Based on our findings in healthy human B cell, we explored whether Brd4 inhibition regulates the differentiation of B cells from patients with SLE, a typical B cell-associated disorder. We first determined the percentages of naïve B cells, memory B cells and plasmablasts in healthy donors and patients with SLE. As shown in Fig.S4, SLE patients exhibited decreased percentages of naïve B cells, and increased percentages of memory B cells and plasmablast compared with healthy donors. We also found increased Brd4 expression in CD19+ B cell from SLE patients compared with those of HC subjects (Fig.S5). Next, we evaluated the effect of Brd4 inhibitors on the differentiation of B cells from SLE patients. Consistent with our findings from healthy donors, we also observed that treatment with PFI-1 decreased the percentages of plasmablasts and plasma cells, but did not influence the percentages of naïve and memory B cells (Fig.5A and B). We further examined the effect of PFI-1 treatment on plasmablast differentiation using an in vitro costimulation method known to induce plasmablasts from peripheral B cells. We observed that, during 7 days in culture, the costimulation resulted in an increase of the percentage of plasmablasts (CD19+IgD-CD38++), and this increase could be decreased by treatment with PFI-1 (Fig.5C and D). In addition, we found that Brd4 inhibitors did not affect the proliferation and apoptosis of CD19+ B cells from patients with SLE (Fig.5E and F).