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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

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Journal Eur J Immunol
Date 2021 Jul 2
PMID 34214192
Citations 3
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Abstract

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.

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References
1.
Keppetipola N, Sharma S, Li Q, Black D . Neuronal regulation of pre-mRNA splicing by polypyrimidine tract binding proteins, PTBP1 and PTBP2. Crit Rev Biochem Mol Biol. 2012; 47(4):360-78. PMC: 3422667. DOI: 10.3109/10409238.2012.691456. View

2.
Kwon K, Hutter C, Sun Q, Bilic I, Cobaleda C, Malin S . Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development. Immunity. 2008; 28(6):751-62. DOI: 10.1016/j.immuni.2008.04.014. View

3.
Chen J, Cai Z, Bai M, Yu X, Zhang C, Cao C . The RNA-binding protein ROD1/PTBP3 cotranscriptionally defines AID-loading sites to mediate antibody class switch in mammalian genomes. Cell Res. 2018; 28(10):981-995. PMC: 6170407. DOI: 10.1038/s41422-018-0076-9. View

4.
Monzon-Casanova E, Matheson L, Tabbada K, Zarnack K, Smith C, Turner M . Polypyrimidine tract-binding proteins are essential for B cell development. Elife. 2020; 9. PMC: 7058386. DOI: 10.7554/eLife.53557. View

5.
Diaz-Munoz M, Bell S, Fairfax K, Monzon-Casanova E, Cunningham A, Gonzalez-Porta M . The RNA-binding protein HuR is essential for the B cell antibody response. Nat Immunol. 2015; 16(4):415-25. PMC: 4479220. DOI: 10.1038/ni.3115. View