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).