Funds to help scientists probe mysteries of plasma cells

Professor David Tarlinton in the lab
with a student

Series about National Health and Medical Research Council (NHMRC) Project Grant recipients in Central Clinical School (CCS) starting in 2019

by Anne Crawford

Professor David Tarlinton’s NHMRC grant will fund research that tackles some of the fundamental questions of B-cell immunology; questions about the cells that produce the antibodies that protect us from infection.

The four-year grant will support new studies by Professor Tarlinton, who heads the Department of Immunology and Pathology at Central Clinical School, into plasma cell survival, investigating various aspects of the cell’s lifespan.

The studies will enlist a manipulated mouse model that took two years to develop and breed. Using what’s called a Cre recombinase, an enzyme that can recombine DNA but in a form that is inducible, the researchers will alter the genome of the mouse at precise times to suit their purposes.

Prof Tarlinton said that their mouse will allow them to change genes inside plasma cells and only plasma cells. “As far as we’re aware it’s the first of its kind in the world and will allow us to uniquely understand the lifespan of the cells that produce the antibodies that protect us from infection.

“This is a whole new area for us, and I think, for the field.”

The mice will be administered a dose of tamoxifen to activate the Cre, causing their plasma cells to become fluorescent red, allowing the researchers to observe the plasma cells that exist in the mouse at the time that they give it the treatment and beyond.

Prof. Tarlinton said the model would enable scientists to measure how the cells behave and answer questions such as ‘do they live for a long time and decay naturally or is turnover driven by production of new plasma cells?’

“None of this has been possible before,” he said.

“These questions are important because this is really what defines the longevity of your immunity to anything you’re exposed to or to a vaccine.

“It might explain why certain auto-immune diseases develop in certain patients because they make too many plasma cells that live for too long,” he said. “It might also reveal that there are plasma cells you make when you’re very young which are really important and which you keep for the rest of your life whereas other ones are not so important and you replace them as you go through your life.

“These are all fundamental questions of immunology that have been very difficult to answer – we’re hoping to provide these answers.”

The scientists will explore what happens with plasma cells and their rate of turnover during chronic disease, what’s at play in poorer immunity in old mice and whether young mice make plasma cells they then keep for their whole life.

“I think it’s going to be really significant,” Prof. Tarlinton said. “Over the past 20 years there’s been one predominant model for how plasma cells survive. The current model is that the old ones are replaced by new ones and that’s how you turn over the population, by constantly making new ones that displace the old ones,” he said.

“Antibody production is one of the key components of the immune system yet we all just assume it behaves in a certain way and that’s never been tested in a quantifiable way.”

Prof. Tarlinton said the NHMRC grant was gratifying as it supported “brand new” work.

“The NHMRC often looks for a degree of completeness in work. Our proposal is actually still very early. They’ve given us the support and hopefully we can now show that it is a great idea!”

For more about Prof. Tarlinton
 https://ccsmonash.blogspot.com/2017/12/never-better-time-for-immunology-says.html
 http://ccsmonash.blogspot.com/2017/10/revealed-enzyme-behind-immune-cell.html
Lab group: www.monash.edu/medicine/ccs/immunology/research/tarlinton-lab