GCB-PRID | Post-transcriptional Regulation of Germinal Center B Cell Responses in Immunity and Disease

Summary
Antibodies secreted by B cells of the adaptive immune system establish an essential barrier against bacteria and viruses and their presence is the hallmark of protective vaccinations. B cells are licensed for their tasks during germinal center (GC) reactions and differentiation into antibody-secreting plasma cells. Unfortunately, B cell-derived autoantibodies and proinflammatory cytokines can cause or contribute to autoimmune diseases.

While major transcription factor networks regulating protective (or pathogenic) GCB cell responses have been identified and characterized, little is known about the post-transcriptional regulation by RNA-binding proteins (RBP), whose number rivals that of transcription factors.
We postulate that RBPs exercise critical post-transcriptional control over germinal center B (GCB) and plasmacytic cell physiology and we aim to identify and molecularly characterize these regulatory mechanisms.

To this end, we will complement sophisticated genetic mouse models with novel cell culture systems. We will monitor RBP activity with fluorescent sensors and use proteomics to reveal RBPs regulating the protein abundance of critical mediators of GCB and plasmacytic cell fates. In addition, we will conduct genetic screens to uncover relevant functions of a short list of 40 RBPs, whose protein expression we found to differ significantly between GCB and mantle zone B cells. Ultimately, we will use cellular immunology and RNA biochemistry to elucidate how these RBPs exert their post-transcriptional control.

Through the integrated power of our multi-disciplinary approach we will thus pinpoint and investigate the functions of key RBPs regulating the biology of GCB and plasmacytic cells. GCB-PRID promises to uncover profoundly new insights into post-transcriptional regulation of adaptive immunity. Thereby, this groundbreaking research aims to reveal novel molecular targets for the treatment of autoimmune diseases, whose incidence is steadily on the rise.
Unfold all
/
Fold all
More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/682435
Start date: 01-09-2016
End date: 31-08-2021
Total budget - Public funding: 1 998 066,00 Euro - 1 998 066,00 Euro
Cordis data

Original description

Antibodies secreted by B cells of the adaptive immune system establish an essential barrier against bacteria and viruses and their presence is the hallmark of protective vaccinations. B cells are licensed for their tasks during germinal center (GC) reactions and differentiation into antibody-secreting plasma cells. Unfortunately, B cell-derived autoantibodies and proinflammatory cytokines can cause or contribute to autoimmune diseases.

While major transcription factor networks regulating protective (or pathogenic) GCB cell responses have been identified and characterized, little is known about the post-transcriptional regulation by RNA-binding proteins (RBP), whose number rivals that of transcription factors.
We postulate that RBPs exercise critical post-transcriptional control over germinal center B (GCB) and plasmacytic cell physiology and we aim to identify and molecularly characterize these regulatory mechanisms.

To this end, we will complement sophisticated genetic mouse models with novel cell culture systems. We will monitor RBP activity with fluorescent sensors and use proteomics to reveal RBPs regulating the protein abundance of critical mediators of GCB and plasmacytic cell fates. In addition, we will conduct genetic screens to uncover relevant functions of a short list of 40 RBPs, whose protein expression we found to differ significantly between GCB and mantle zone B cells. Ultimately, we will use cellular immunology and RNA biochemistry to elucidate how these RBPs exert their post-transcriptional control.

Through the integrated power of our multi-disciplinary approach we will thus pinpoint and investigate the functions of key RBPs regulating the biology of GCB and plasmacytic cells. GCB-PRID promises to uncover profoundly new insights into post-transcriptional regulation of adaptive immunity. Thereby, this groundbreaking research aims to reveal novel molecular targets for the treatment of autoimmune diseases, whose incidence is steadily on the rise.

Status

CLOSED

Call topic

ERC-CoG-2015

Update Date

27-04-2024
Images
No images available.
Geographical location(s)
Structured mapping
Unfold all
/
Fold all
Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.1. EXCELLENT SCIENCE - European Research Council (ERC)
ERC-2015
ERC-2015-CoG
ERC-CoG-2015 ERC Consolidator Grant