Australian researchers make immune system breakthrough

Researchers from Melbourne’s Walter and Eliza Hall Institute (WEHI) have published the results of a study overturning conventional wisdom about how the body’s B cells form the memories which help them to fight off infections.

B cells produce the antibodies which fight infection, while memory B cells are responsible for maintaining protection following immunisation. But before developing into memory cells, they must first survive the natual process of apopstosis, otherwise known as programmed cell death, which normally occurs in the wake of a major immune response.

For the last few years, Associate Professor David Tarlinton and Dr Ingela Vikstrom from the institute’s Immunology division have been studying the specific proteins which regulate B cell survival, and from where they receive their instructions to either live or die. Their work focussed on the two key pro-survival proteins Bcl-xL and Mcl-1, the former of which has long been assumed to play the dominant role in instructing B cells and apopstosis.

What their research has shown however is that the opposite is true.

“We used genetic and pharmacological methods to identify which pro-survival molecules were essential for the process of ‘instructing’ these cells to establish germinal centres, as well as instructing activated B cells to proliferate and differentiate into memory B cells,” Dr Vikstrom said.

“It surprised us to find that, contrary to popular belief, Mcl-1 is the essential pro-survival protein required for creation and maintenance of B cell memory.”

The discovery has important implications for cancer treatment given that cancerous cells often arise from unregulated cell growth when apopstosis fails to occur. The researchers also noted that this new understanding could help in the treatment of autoimmune disease as well as potentially reducing the risks of transplant rejection.

“All cells have the potential to undergo apoptosis, so developing our understanding of the major proteins responsible for this process will have applications to all cell types in the body,” said Dr Tarlinton.

The study, which appeared in today’s issue of Science was supported by the National Health and Medical Research Council, the Leukaemia and Lymphoma Society, and the US National Institutes of Health, build on a paper Drs Tarlinton and Vikstrom published earlier this year in Proceedings of the National Academy of the Sciences, with institute researchers Dr Andrew Lew and Dr Emma Carrington. Using a molecule that blocked the action of Bcl-xL, the study revealed that Bcl-xL was not necessary for the development of germinal centres - cellular structre where B cells form - and memory B cells, indicating that another pro-survival protein – now shown to be Mcl-1 – was the key to survival.

The work was supported by the National Health and Medical Research Council (NHMRC), the Leukaemia and Lymphoma Society, and the US National Institutes of Health.