David Tarlinton, PhD

David TarlintonDavid Tarlinton, PhD

The Walter and Eliza Hall Institute of Medical Research
Melbourne, Australia.
Title: Attacking the source: targeting plasma cell survival in lupus

The Study and What It Means to Patients

“Our project targets the cells that produce the disease-causing autoantibodies in lupus. The life span of these antibody secreting cells, which are called plasma cells, is normally controlled by a protein inside them called Lyn. In lupus, harmful plasma cells survive, possibly due to abnormally low levels of Lyn.  We will search for drug candidates that can remove these plasma cells by mimicking the effects of Lyn.”


Antibodies usually protect us but can attack our own tissues and organs and then they cause disease. Such auto-antibodies contribute to lupus and making them go away would greatly reduce the symptoms. It is difficult to remove the auto-antibodies, however, as the cells that make them are very rare and difficult to kill. We think we have discovered a way to kill these cells and that if this works, it could be used to make new, effective medicines for lupus.

Scientific Abstract

In SLE, auto-antibody titres correlate with disease severity and responsiveness to therapy. Removing pathogenic plasma cells and thus reducing auto-reactive antibodies would have clinical benefit. We therefore propose the development of a novel strategy to target plasma cell survival, potentially restricted to those secreting pathogenic antibodies. Using Lyn- deficient mice, a well-characterized model of SLE, we have discovered that Lyn is a crucial negative regulator of plasma cell survival, controlling responsiveness to key survival factors.

We propose to investigate this hyper-responsiveness, identifying the signaling pathways controlled by Lyn and thus the signaling molecules that control plasma cell survival. We will use our unique ability to recover plasma cells from inflamed tissues in Lyn mice to determine if they have unique survival characteristics and pathways. We will screen kinase inhibitors on pathogenic and total plasma cells to determine their sensitivity to such inhibition. Collectively this information will allow us to isolate the components of the survival pathways, using plasma cell lines we will make. Finally, our mouse results will be verified in plasmablasts from both controls and SLE patients. Thus we will identify therapeutic targets that will kill plasma cells in SLE.