Secrets of Immunity

By Gia Scafidi, USC News Service

Since its discovery in 1999, an enzyme vital to the body’s immune response had bewildered scientists. All evidence suggested that the enzyme, called AID, generated genetic mutations in immune cells necessary to produce the high-affinity antibodies that target and kill pathogens. Despite intense efforts, scientists had failed to demonstrate AID’s biochemical activity on DNA or RNA, the molecules that encode genetic information.

In April, USC College scientists showed for the first time that AID interacts with single-stranded DNA, and revealed why so many others had failed. In an experiment to see if AID would act on a DNA-RNA molecule, postdoctoral researcher Ronda Bransteitter mixed in an enzyme that clips away RNA (RNAase). To the team’s surprise, AID became active. “By adding RNAase, Ronda got rid of an RNA-inhibitor that had been hindering AID’s activity,” says Myron Goodman, professor of biology and chemistry, noting that the previously unknown inhibitor was what had kept others from making the discovery.

The finding brings researchers closer to understanding exactly how the immune system defends the body against disease-causing viruses, bacteria and other agents. “Children without this enzyme die of infections at very young ages due to their inability to produce high-affinity antibodies,” says Goodman, who co-authored a report on the work with lead author Bransteitter, postdoctoral researcher Phuong Pham and Matthew Scharff of the Albert Einstein College of Medicine. AID also helps the body to remember past attacks, which enables vaccines to work.