The immune system produces a huge variety – hundreds of billions – of high-affinity antibodies. Immunologists have been asking how B cells accomplish this for decades, and in the past five years, the answers have come, all in a rush. A single enzyme, it appears, mutates DNA to control two very different diversifying phenomena: hypermutation of the variable region and class switch recombination.
"It's beautiful because there's this really old problem and it's finally solved," says Michel Nussenzweig, a molecular immunologist at Rockefeller University in New York City. "And it's solved in such a minimal way," he adds, with one enzyme and three reactions.
The enzyme, activation induced deaminase (AID), was described in 2000.1 Early evidence that DNA, rather than RNA, was the substrate appeared in 2002.2 The next logical step was to make the enzyme work in a biochemical assay. Three of this issue's four Hot Papers used unconventional ...
