New role for antibodies discovered

University of Otago researchers have found that antibodies – the immune system’s frontline fighters – also play an unexpected behind-the-scenes role in kick starting the body’s immune response.

The highly soluble blood proteins are well known as essential weapons in fighting pathogens such as bacteria, fungi and viruses through binding to and destroying the invaders.

Now, in a ground-breaking discovery, researchers from the University’s Dunedin and Christchurch campuses have shown that antibodies are also recycled in a lipid particle form to enhance the body’s immune response when infection first strikes. The study appeared in the prestigious Journal of Immunology.

Department of Microbiology and Immunology senior lecturer Dr Alexander McLellan says the improved understanding of the immune system this research provides may lead to further improvements in vaccine design.

"Our finding goes some way to explain the largely unsolved mystery of how the immune system gets kick-started. A major outstanding problem in immunology is how small amounts of infectious material can trigger strong immune responses at the start of the infection," Dr McLellan says.

Antibodies are released by specialised white blood cells, called B cells, following vaccination or previous exposure to pathogens and circulate around the body to provide long lasting protection in the blood and solid organs.

Dr McLellan’s research group has now shown that B cells use antibody to pull in tiny fragments of pathogens bound to the cell’s surface and then recycle these to amplify the immune response.

"Instead of destroying these fragments, we were surprised to find that B cells send them out again, still bound to antibody in a lipid particle, to further stimulate the immune system."

The recycled pathogen fragments on these specialised antibody particles trigger other white blood cells involved in initiating the immune response. This contrasts with the extensively studied function of the highly soluble form of antibody, which is known to function exclusively to destroy pathogens, he says.

"We believe our discovery of this recycling mechanism goes someway to explain why the immune system is an incredibly powerful bio-sensor, able to detect nanograms of pathogen material. Essentially, this is same as being able to taste half a teaspoon of instant coffee dissolved in an Olympic swimming pool, such as Dunedin’s Moana Pool."

To identify the type of white blood cells involved in the release of the specialised antibody particles, the research group used a sophisticated machine called a flow cytometer.

This $1m state-of-the-art piece of equipment enables high speed purification of cells from complex mixtures, such as blood cell suspensions.

(Source: Journal of Immunology: University of Otago: July 2008)