How our cells play ‘molecular roulette’ to fight disease

How our cells play ‘molecular roulette’ to fight disease

Illuminate newsletter header, Autumn 23
March 2023
Researchers have revealed the surprisingly random way the immune system defends against infection and disease.

A new study has shown cells responsible for making antibody proteins use a randomisation process to determine which type of antibody to make – behaviour that scientists have dubbed “molecular roulette”. This finding has led to crucial modelling that could reveal which individuals are biologically prone to developing diseases like asthma, autoimmune conditions and infections.

Milestone discovery

Dr Miles Horton (L) and Professor Phil Hodgkin (R)
have unravelled the first mathematical model that
could predict the type and amount of antibody that
will be produced.

Antibodies produced by immune cells protect the body against disease by alerting the immune system to foreign invaders like bacteria and viruses.

B cells (or B lymphocytes) are a type of immune cell that produce five different classes of antibodies, each tailored to attack a specific pathogenic organism.

Chief investigator Professor Phil Hodgkin said the team was surprised to discover that B cells use a randomisation process to choose which antibodies to make.

Instead of instructing every cell what to do, as previously thought, our B cells are effectively running a little casino behind the scenes,” Professor Hodgkin, Head of Immunology at WEHI, said.

“Ultimately B cells play a kind of molecular roulette to allocate a certain number of cells to each antibody class."

“This milestone discovery is a significant step towards understanding how these varying probabilities impact an individual’s likelihood of developing certain diseases, while also broadening our understanding of how cells behave at the molecular level.”

Crucial predictions

The finding has been leveraged to create a mathematical formula that brings researchers the closest they’ve yet been to accurately predicting which antibody class a B cell will make, when the antibody will be made and whether a cell will choose to make a specific antibody class over another.

“This is crucial because we know certain autoimmune conditions and infections can be triggered if this allocation process goes awry and the wrong type of antibody is made,” lead author Dr Miles Horton explained.

“Our precise formula is a pivotal starting point in understanding how an individual’s molecular roulette tables (or genetic variations) can influence their predetermined likelihood of developing certain conditions like asthma – a disease derived from a specific antibody class.”

Through this research, the team hopes to begin exploring how the immune system can be manipulated for therapeutic benefit in the future, to prevent this allocation process going wrong.