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).