B-lymphocytes in Autoimmunity and Malignancies

The B-lymphocytes in Autoimmunity and Malignancies Laboratory studies the immunobiology of B-lymphocytes, particularly the B cell survival factors BAFF and APRIL and their receptors BAFF-R, TACI and BCMA.

Professor Fabienne Mackay has shown that excess BAFF leads to autoimmunity in mice and is associated with human autoimmunity, in particular systemic lupus erythematosus (SLE). This has encouraged the development of Belimumab, a therapeutic BAFF-blocking antibody that has been approved for use in SLE in the clinic. The laboratory’s effort has been extended to understand how dietary interventions lower the risk of developing SLE and how diet/dietary metabolites can be used as therapeutic modalities.

Another research area of the lab is chronic lymphocytic leukaemia (CLL), a blood cancer caused by the clonal expansion of mature B cells. Patients with CLL show severe systemic immunodeficiency that results in death in a quarter of CLL patients despite therapeutic intervention. Our laboratory has shown that CLL cells rely on BAFF/APRIL to suppress the immune system through IL-10 production.

We aim to identify novel therapeutic targets that will be able to restore patient immune function in CLL and halt CLL progression. Hence, the laboratory is developing a therapeutic antibody against CLL which would not compromise the host’s protective immunity.

In an attempt to identify a novel therapeutic target for CLL, we have identified that a fat-rich diet halts CLL progression. We are now investigating the cellular and molecular mechanism underlying this protection against CLL.

• National Health and Medical Research Council
• Lupus Research Alliance
• CSL Research Acceleration Initiative