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Gizlenci, O.

Publications and source records attributed to Gizlenci, O..

2 recordsLinked to original sources

An integrated proteome and transcriptome of B cell maturation defines poised activation states of transitional and mature B cells

During B cell maturation, transitional and mature B cells acquire cell-intrinsic features that determine their ability to exit quiescence and mount effective immune responses. We used label-free mass spectrometry to quantify the proteome of B cell subsets from the mouse spleen and map the differential expression of environmental sensing, transcription- and translation initiation-factors that define cellular identity and function. By comparing the full-length transcriptome and proteome within the same sample, we identified mRNAs linked to B cell activation and antibody secretion that are expressed without detectable protein. These "poised" mRNAs might enable rapid protein production through increased translation or protein stability. In addition, through interrogation of our proteomic dataset, we found that the translational repressor PDCD4 restrains the response of marginal zone B cells to a T-independent antigen. Our molecular characterization of B cell maturation is a valuable resource to further explore the mechanisms underpinning the specialised functions of B cell subsets.

immunology↗

Polypyrimidine Tract Binding Protein 1 regulates the activation of mouse CD8 T cells

We show that the RNA-binding protein Polypyrimidine Tract Binding Protein 1 (PTBP1) is dispensable for the development of naive mouse CD8 T cells, but is necessary for the optimal expansion and production of effector molecules by antigen-specific CD8 T cells in vivo. PTBP1 has an essential role in regulating the early events following activation of the naive CD8 T cell leading to IL-2 and TNF production. It is also required to protect activated CD8 T cells from apoptosis. PTBP1 controls alternative splicing of over 400 genes in naive CD8 T cells in addition to regulating the abundance of [~]200 mRNAs. PTBP1 is required for the nuclear accumulation of c-Fos, NFATc2 and NFATc3, but not NFATc1. This selective effect on NFAT proteins correlates with PTBP1-promoted expression of the shorter A{beta}1 isoform and exon 13 skipped A{beta}2 isoform of the catalytic A-subunit of calcineurin phosphatase. These findings reveal a crucial role for PTBP1 in regulating CD8 T cell activation.

immunology↗