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

Eur J Immunol. 2021 Sep;51(9):2266-2273. doi: 10.1002/eji.202149257. Epub 2021 Jul 26.


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 self-reactivity. 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.

Keywords: PTBP1; PTBP3; RNA binding proteins; mature B cells; posttranscriptional gene expression regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alternative Splicing / genetics
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • Gene Expression Regulation / genetics*
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polypyrimidine Tract-Binding Protein / genetics*
  • Polypyrimidine Tract-Binding Protein / metabolism
  • Signal Transduction / immunology
  • Transcriptome / genetics


  • 3' Untranslated Regions
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Ptbp1 protein, mouse
  • Polypyrimidine Tract-Binding Protein