Effect of Brd4-CKO on nephritis and percentages of plasma cells
in mice with pristane-induced lupus model
Pristane-induced glomerulonephritis in C57BL/6 mice is similar to the
same autoantibodies typically observed in human lupus. We next evaluated
the severity of nephritis in pristane-induced WT and Brd4-CKO mice. We
observed that pristane-induced proteinuria was reduced in Brd4-CKO mice
compared to WT mice (Fig. 6I). We further demonstrated an attenuation of
kidney histologic damage using light microscopic examination in Brd4-CKO
mice, as evidenced by a reduction in glomerular size, inhibition of
mesangial expansion, and reduced cellularity (Fig. 6J).
To determine the impact of Brd4 deficiency on pristane-induced
hypergammaglobulinemia, serum was collected at baseline and every month
after pristine administration for 6 months. The serum levels of total
IgG, IgG1, and IgG2a were significantly reduced in Brd4-CKO mice
compared to WT (FL/FL) mice at 6 months after pristane injection (Fig.
S8).
To further evaluate the effect of Brd4 deficiency on the frequency of
plasma cells in mice with pristane-induced lupus model, B cells were
isolated from lymph node, PBMCs and spleen of mice. Flow cytometric
analysis showed significant reduction of plasma cells
(CD19+/-CD138+) from the lymph
nodes, PBMC and spleens of Brd4-CKO mice compared to WT (FL/FL) mice
(Fig. 6K).