MUrine Tools to Catch High Affinity Plasma cells (MUTCHAP)
Lead Research Organisation:
University of Birmingham
Department Name: Sch of Biosciences
Abstract
Immunoglobulin affinity maturation happens in the germinal centre (GC). We recently described a population of plasma cells emerging from GCs at specific times after vaccination (Meyer-Hermann et al., Cell Rep, 2012). However, there are currently no known markers specifically identifying this population.
We plan to identify GC derived plasmablasts using genetic engineering of mice to induce fluorescent proteins being activated during plasma cell generation. This should lead to a novel mouse model which can identify GC cells that recently entered plasma cell differentiation, following immunisation or infection. The mice can be used as models to study plasma cell differentiation from the germinal centre, their migration in live tissues using intravital light sheet microscopy, or aid their isolation so that gene and protein expression can be studied on single cell level.
This project will test the hypothesis that these plasma cells are key components producing long term high affinity antibody responses. Further, we will test which signals are regulating their appearance. This may also lead to new ways of generating more efficiently monoclonal antibody drugs.
We plan to identify GC derived plasmablasts using genetic engineering of mice to induce fluorescent proteins being activated during plasma cell generation. This should lead to a novel mouse model which can identify GC cells that recently entered plasma cell differentiation, following immunisation or infection. The mice can be used as models to study plasma cell differentiation from the germinal centre, their migration in live tissues using intravital light sheet microscopy, or aid their isolation so that gene and protein expression can be studied on single cell level.
This project will test the hypothesis that these plasma cells are key components producing long term high affinity antibody responses. Further, we will test which signals are regulating their appearance. This may also lead to new ways of generating more efficiently monoclonal antibody drugs.
Publications
Zhang Y
(2018)
Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells.
in The Journal of experimental medicine
Price Michael John
(2021)
MUrine tools to catch high-affinity plasma cells (MUTCHAP)
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
BB/M01116X/1 | 30/09/2015 | 31/03/2024 | |||
1943417 | Studentship | BB/M01116X/1 | 02/10/2016 | 25/03/2021 | Michael Price |
Description | Provision of GM mice |
Organisation | RIKEN |
Department | RIKEN Center for Integrative Medical Sciences (IMS) |
Country | Japan |
Sector | Private |
PI Contribution | Provision of mice that can be used to track germinal centre B cells |
Collaborator Contribution | Provision of mice that have an inducible expression of Cre recombinase under the control of the S1PR2 promotor |
Impact | We currently use these mice to generate new unique mouse models to study germinal centre B cell differentiation. |
Start Year | 2018 |