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Genetic analysis of factors that regulate mRNA stability in the development of B cells

Reference	BB/C506121/1
Principal Investigator / Supervisor	Dr Martin Turner
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	214,152
Status	Completed
Type	Research Grant
Start date	01/02/2005
End date	31/03/2008
Duration	38 months

Abstract

Upon antigen encounter mature B lymphocytes proliferate and enter the germinal centre reaction where they undergo iterative rounds of somatic hypermutation, selection and Ig class switching. An alternative cell fate decision for mature B cells Is differentiation into the antibody secreting plasma cell. Transcriptional repression of genes necessary for plasma cell differentiation partially explains the molecular basis of this cell fate decision. However this cannot account for the rapid removal of mRNA encoding lineage specific transcripts upon differentiation. This must be mediated at the post-transcriptional level to ensure the rapid generation of effector and memory cells both during and following infection. In this study we propose to test the hypothesis that RNA binding proteins of the TIS11/BRF family mediate this function in B cells. These genes are rapidly induced upon B cell activation and bind AU rich elements found in the 3¿UTR of mRNA¿s triggering their degradation. ARE motifs are found in the 3¿UTR of many key mRNA species involved in germinal centre and plasma cell differentiation. We will approach this problem by using monoclonal antibodies to track expression of the proteins in individual cells and in histological sections during an immune response. Furthermore we will specifically mutate TIS11b/BRF1 in B lymphocytes using a conditional gene targeting approach. The development of B cells will then be measured in both naive and immunised mice.

Summary

unavailable

Committee	Closed Committee - Animal Sciences (AS)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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