The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers

Monzón-Casanova, Elisa; Screen, Michael; Díaz-Muñoz, Manuel D.; Coulson, Richard M. R.; Bell, Sarah E.; Lamers, Greta; Solimena, Michele; Smith, Christopher W.J.; Turner, Martin

doi:10.1038/s41590-017-0035-5

Cited by 70 publications

(107 citation statements)

References 65 publications

(98 reference statements)

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“…Therefore, PTBP1 protein expression was similar between the different bone marrow B cell populations. PTBP3 protein detected with a specific monoclonal antibody (Monzon-Casanova et al, 2018) was also relatively constant throughout B cell development ( Supplementary Fig. 1c, d).…”

Section: Redundancy Between Ptbp1 and Ptbp2 For B Cell Developmentmentioning

confidence: 84%

“…As both PTBP1 and PTBP3 are expressed in mature B cells (Monzon-Casanova et al, 2018) we determined their expression during defined stages of B cell development in mouse bone marrow (Supplementary Fig. 1a-d).…”

Section: Redundancy Between Ptbp1 and Ptbp2 For B Cell Developmentmentioning

confidence: 99%

“…PTBP1 suppresses expression of PTBP2 directly by inducing Ptbp2 exon 10 skipping and mRNA degradation by NMD (Boutz et al, 2007). In germinal centre B cells, PTBP1 promotes proliferation, the c-MYC gene expression program induced upon positive selection and antibody affinity maturation (Monzon-Casanova et al, 2018). PTBP1 and PTBP2 have specific and redundant functions (Spellman et al, 2007;Vuong et al, 2016;Ling et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…PTBP1 and PTBP2 have specific and redundant functions (Spellman et al, 2007;Vuong et al, 2016;Ling et al, 2016). Therefore, expression of PTBP2 in PTBP1-deficient cells compensates for many functions of PTBP1 (Spellman et al, 2007;Vuong et al, 2016;Ling et al, 2016;Monzon-Casanova et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…To study the roles of PTBP1 controlling post-transcriptional gene expression in B cells, we and others deleted Ptbp1 in pro-B cells and found normal B cell development accompanied by PTBP2 expression (Monzon-Casanova et al, 2018;Sasanuma et al, 2019). Here we addressed the functions of PTBP in B cell development by deleting both Ptbp1 and Ptbp2 in pro-B cells.…”

Section: Introductionmentioning

confidence: 99%

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Polypyrimidine Tract Binding Proteins are essential for B cell development

Monzón-Casanova

Matheson

Tabbada

et al. 2019

Preprint

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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.

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Section: Redundancy Between Ptbp1 and Ptbp2 For B Cell Developmentmentioning

confidence: 84%

Section: Redundancy Between Ptbp1 and Ptbp2 For B Cell Developmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Polypyrimidine Tract Binding Proteins are essential for B cell development

Monzón-Casanova

Matheson

Tabbada

et al. 2019

Preprint

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

et al. 2021

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The maturation of immature B cells and the survival of mature B cells is stringently controlled to maintain a diverse repertoire of antibody specificities while avoiding selfreactivity. At the molecular level this is regulated by signaling from membrane Ig and the BAFF-receptor that sustain a pro-survival program of gene expression. Whether and how posttranscriptional mechanisms contribute to B cell maturation and survival remains poorly understood. Here, we show that the polypyrimidine tract binding proteins (PTBP) PTBP1 and PTBP3 bind to a large and overlapping set of transcripts in B cells. Both PTBP1 and PTBP3 bind to introns and exons where they are predicted to regulate alternative splicing. Moreover, they also show high-density of binding to 3' untranslated regions suggesting they influence the transcriptome in diverse ways. We show that PTBP1 and PTBP3 are required in B cells beyond the immature cell stage to sustain transitional B cells and the B1, marginal zone and follicular B cell lineages. Therefore, PTBP1 and PTBP3 promote the maturation of quiescent B cells by regulating gene expression at the posttranscriptional level.

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Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells

et al. 2022

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The RNA-binding protein polypyrimidine tract binding protein 1 (PTBP1) has been found to have roles in CD4 T-cell activation, but its function in CD8 T cells remains untested. We show it is dispensable for the development of naïve mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naïve CD8 T cell leading to IL-2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naïve CD8 T cells in addition to regulating the abundance of ∼200 mRNAs. PTBP1 is required for the nuclear accumulation of c-Fos, NFATc2, and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1-promoted expression of the shorter Aβ1 isoform and exon 13 skipped Aβ2 isoform of the catalytic A-subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T-cell activation.

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The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers

Cited by 70 publications

References 65 publications

Polypyrimidine Tract Binding Proteins are essential for B cell development

Polypyrimidine Tract Binding Proteins are essential for B cell development

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

Polypyrimidine tract binding protein 1 regulates the activation of mouse CD8 T cells

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