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Flow Cytometric Characterization of Murine B Cell Development
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Polypyrimidine tract-binding proteins are essential for B cell development.

Elisa Monzón-Casanova1,2, Louise S Matheson1, Kristina Tabbada3

  • 1Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.

Elife
|February 22, 2020
PubMed
Summary
This summary is machine-generated.

Polypyrimidine tract-binding protein 1 (PTBP1) is crucial for B cell development. Its absence leads to PTBP2 compensation, but deleting both PTBP1 and PTBP2 blocks B cell maturation at the pro-B stage.

Keywords:
B cell developmentRNA-binding proteinsalternative splicingcell cyclechromosomesgene expressionimmunologyinflammationmouse

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein (RBP) vital for B cell development.
  • PTBP1 regulates gene expression post-transcriptionally.

Purpose of the Study:

  • To investigate the role of PTBP1 and PTBP2 in B cell ontogeny.
  • To elucidate the mechanism by which PTBP1 controls cell cycle progression in pro-B cells.

Main Methods:

  • Gene deletion studies in mouse models (Ptbp1 and Ptbp2).
  • Analysis of B cell development stages.
  • Assessment of cell cycle regulation and mRNA splicing.

Main Results:

  • Deletion of Ptbp1 leads to PTBP2 upregulation and normal B cell development, indicating PTBP2 compensation.
  • Simultaneous deletion of Ptbp1 and Ptbp2 causes a complete block at the pro-B cell stage.
  • PTBP1 regulates cell cycle progression by controlling cyclin-dependent kinases, suppressing S-phase entry, and promoting mitosis.
  • PTBP1 influences mRNA levels and alternative splicing of key cell cycle regulators like CYCLIN-D2, c-MYC, p107, and CDC25B.

Conclusions:

  • PTBP2 compensates for PTBP1 loss during B cell development.
  • PTBP1 is essential for B cell ontogeny, controlling cell cycle progression at the pro-B stage.
  • PTBP1 integrates transcriptional and post-translational control of cell cycle progression through RNA binding.