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

European Journal of Immunology - Tập 51 Số 9 - Trang 2266-2273 - 2021
Elisa Monzón‐Casanova1,2, Kirsty J. Bates2, Christopher W. J. Smith1, Martin Turner2
1Department of Biochemistry, University of Cambridge, Cambridge, UK
2Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge, UK

Tóm tắt

AbstractThe 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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Tài liệu tham khảo

10.1084/jem.190.1.75

10.4049/jimmunol.167.12.6834

10.3389/fimmu.2018.02285

10.1016/j.ceb.2017.10.002

10.1038/ni.3724

10.3389/fimmu.2018.01094

10.3109/10409238.2012.691456

Monzon‐Casanova E., 2018, The RNA‐binding protein PTBP1 is necessary for B cell selection in germinal centers, Nat. Immunol., 45, 471

10.1093/intimm/dxy077

Monzon‐Casanova E., 2020, Polypyrimidine tract‐binding proteins are essential for B cell development, eLife Sciences, 9, 613

10.1093/nar/gkv429

Chen J., 2018, The RNA‐binding protein ROD1/PTBP3 cotranscriptionally defines AID‐loading sites to mediate antibody class switch in mammalian genomes, Cell Res., 302, 575

10.1038/nsmb.1838

10.1261/rna.5229704

10.1073/pnas.0605944103

10.1371/journal.pone.0197973

10.1016/j.immuni.2008.04.014

10.4049/jimmunol.170.12.5820

10.1016/j.celrep.2016.11.034

10.1371/journal.pone.0016992

10.1002/eji.201970107

10.1093/bioinformatics/bts635

10.1038/ni.3115

Thông tin
Thông tin xuất bản

European Journal of Immunology

Tập 51 Số 9

2266-2273

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