Analysis of the role of BAFF-R in T cell responses

This project is suitable for an Honours or Masters student.

BACKGROUND

The Mackay lab investigates the immunobiology of B-lymphocytes, particularly the B cell survival factors BAFF and APRIL, and their receptors BAFF-R, TACI and BCMA. The role of BAFF-R signalling in the maintenance of B cells is very well studied. However, even though it has been established that BAFF-R is expressed on T cells (regulatory T cells in particular), little is known about what role this receptor plays in T cell immunology.

BAFF co-stimulation promotes T cell activation with cytokine production via BAFF-R both in-vitro and in-vivo. To understand the function of BAFF-R expression on CD4 T cells, we have generated a mouse line in which BAFF-R is specifically deleted in CD4 T cells. This project will investigate whether BAFF-R expression on CD4 T cells is critical for an antibody response in a T-cell dependent immunisation model.

Given that there are therapeutics available that inhibit BAFF-to-BAFF-R signalling, this is an important avenue of investigation. The results obtained in this project will be applied to develop novel therapeutics for the treatment of B cell dependent autoimmune diseases.

AIMS

• Explore the different T cell subsets where BAFF-R is expressed.
• Explore the role of BAFF-R in thymic T cell development
• Explore the role of BAFF-R in T cell activation.
• Investigate the role of BAFF-R expression in the immune response.

Through these studies, the student will gain significant expertise in mouse models of disease, cell culture, flow cytometry, immunohistochemistry and other laboratory techniques.

PROJECT POTENTIAL

To pioneer knowledge in a neglected area of immunology, validate these findings with human immune cells and publish a high impact, world-first discovery.