Polypyrimidine Tract Binding Proteins are essential for B cell development

Abstract

During B cell development, recombination of immunoglobulin loci is tightly coordinated with the cell cycle to avoid unwanted rearrangements of other genomic locations. Several factors have been identified that suppress proliferation in late-pre-B cells to allow light chain recombination. By comparison, our knowledge of factors limiting proliferation during heavy chain recombination at the pro-B cell stage is very limited. Here we identify an essential role for the RNA-binding protein Polypyrimidine Tract Binding Protein 1 (PTBP1) in B cell development. Absence of PTBP1 and the paralog PTBP2 results in a complete block in development at the pro-B cell stage. PTBP1 promotes the fidelity of the transcriptome in pro-B cells. In particular, PTBP1 controls a cell cycle mRNA regulon, suppresses entry into S-phase and promotes progression into mitosis. Our results highlight the importance of S-phase entry suppression and post-transcriptional gene expression control by PTBP1 in pro-B cells for proper B cell development.

Single-cell RNA-seq analysis reveals penaeid shrimp hemocyte subpopulations and cell differentiation process

“…For examples, sin3 histone deacetylase corepressor complex component SDS3 (SUDS3) (Mj-9135) and histone deacetylase (HDAC) (Mj-18057) are known to be essential for the proliferation through controlling cell cycle progression, DNA replication and repair, and cell death in mammal studies (28,29). Polypyrimidine tract-binding protein 1 (PTBP1) (Mj-18644) is also genes related to cell proliferation, cell migration, and colony formation in human tumor studies (30)(31)(32). It is a multi-functional RNA-binding protein that is overexpressed in glioma, a type of tumor that occurs in the brain, and a decreased expression of PTBP inhibits cell migration and increases the adhesion of cells to fibronectin and vitronectin (30,31).…”

Splice Factor Polypyrimidine tract-binding protein 1 (Ptbp1) is Required for Immune Priming of the Endothelium in Atherogenic Disturbed Flow Conditions

“…coronary, tibial, aorta) revealed a strong conservation of gene-gene interactions between arteries (Figure 6I), but that genes correlated with Ptbp1 in arteries did not have the same correlation in whole blood (Figure 6J). We then asked what gene groups are most often positively correlated with Ptbp1 expression, and found a strong signature for Myc (which can induce Ptbp1 expression, and is also regulated by Ptbp1 24–26 ), but also Interferon gamma signaling, and TNF signaling via NFκB (Figure 6K&L and SI Table).…”

Essential requirement for polypyrimidine tract binding proteins 1 and 3 in the maturation and maintenance of mature B cells in mice

“…The requirement of both PTBP1 and PTBP3 in transitional and mature B cells contrasts with early B cell development where PTBP2 compensated completely for the absence of these proteins [10]. In mouse brain, PTBP1 and PTBP2 bind redundantly largely to the same sites [19].…”

“…Knowledge of PTBP3 in physiological systems is limited with a report that Ptbp3 -/mice have normal B cell development, but defective antibody responses [12]. However, when Ptbp3 was deleted conditionally in B cells with the Cd79a Cre allele we found normal B cell development, antibody amounts, and affinity maturation in response to immunization ( [10] and unpublished data). Here, we show that PTBP1 and PTBP3 act redundantly to promote the maturation and maintenance of B cells.…”

“…Absence of PTBP1 in B cells led to the expression of PTBP2 [8], which is expressed in the brain [7]. In mice with Cd79a Cre -mediated conditional deletion of both Ptbp1 and Ptbp2, B cell development is blocked at the pro-B cell stage [10]. This is associated with defective cell cycle regulation in pro-B cells and shows that PTBP2, which is silenced by PTBP1, compensates for the lack of PTBP1.…”