Multifunctional role of the transcription factor Blimp1 in coordinating plasma cell differentiation

Blimp1 is an essential regulator of plasma cells. Here we studied its functions in early plasmablast differentiation by identifying regulated Blimp1 target genes. Blimp1 promoted plasmablast migration and adhesion by controlling many genes involved in these processes. It repressed several transcription factor genes and Aicda, thus silencing B-cell-specific gene expression, antigen presentation and class switch recombination in plasmablasts. It also directly activated genes, leading to increased expression of the plasma cell regulator IRF4 and proteins involved in immunoglobulin secretion. Blimp1 strongly induced immunoglobulin gene transcription by controlling the activity of Igh and Igk 3’ enhancers and regulated the posttranscriptional switch of expression from the membrane-bound to secreted immunoglobulin heavy-chain by activating Ell2. Notably, Blimp1 recruited chromatin-remodeling and histone-modifying complexes to regulate its target gene. Hence, many essential functions of plasma cells are under Blimp1 control. 40 samples in total: A) 16 RNA-Seq samples in 5 cell types: Activated B cells (Act B cell, 2 replicates), Pre-Plasmablasts (Pre-PB, 3 genotypes, 2-4 replicates each), Plasmablasts (PB, 2 replicates), Plasma cells (2 replicates), Mature B cells (2 replicates); B) 19 ChIP-Seq samples in 3 cell types: Act B cell (IRF4, H3K9ac, H3K4me2, H3K4me3, 1 replicate each; H3K27me3, 2 genotypes, 2 and 1 replicates), Pre-PB (IRF4, 1 replicate; H3K27me3, 2 genotypes, 1 replicate each), PB ( PU.1, IRF4, H3K9ac, H3K4me2, H3K4me3, 1 replicate each; Blimp1, H3K27me3, 2 replicates each); C) 5 ATAC-Seq samples in 3 cell types: Act B cell (2 genotypes, 1 replicate each), Pre-PB (2 genotypes, 1 replicate each), PB (1 replicate).