Repository logo
 

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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Monzón-Casanova, Elisa 
Bates, Kirsty J 
Smith, Christopher WJ 

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.

Description

Keywords

PTBP1, PTBP3, RNA binding proteins, mature B cells, posttranscriptional gene expression regulation, 3' Untranslated Regions, Alternative Splicing, Animals, B-Lymphocytes, Gene Expression Regulation, Heterogeneous-Nuclear Ribonucleoproteins, Mice, Mice, Inbred C57BL, Mice, Knockout, Polypyrimidine Tract-Binding Protein, Signal Transduction, Transcriptome

Journal Title

Eur J Immunol

Conference Name

Journal ISSN

0014-2980
1521-4141

Volume Title

51

Publisher

Wiley

Rights

All rights reserved
Sponsorship
Biotechnology and Biological Sciences Research Council (BB/J001457/1)