As it fights off an infection, the human body tailors its immune response. For example, in a process known as class switch recombination, immune cells called B cells rearrange their DNA.
In so doing, they alter the antibodies they’re making, so the Y-shaped molecules speed to specific tissues of the body rather than simply circulate in the blood.
“Without class switch recombination, we wouldn’t be able to send antibodies across the gastrointestinal tract or into the lungs,” notes Michael R. Lieber of the University of Southern California Keck School of Medicine in Los Angeles.
In the May 12 Science, Lieber and his colleagues report observations of unusual RNA-DNA hybrids that may help resolve how B cells perform this crucial DNA exchange. To shift from making a generic antibody destined for the bloodstream, a B cell selects a new gene to build the stem of the Y-shaped protein. The B cell has several genes to choose from, each with a DNA sequence called a switch region in front of it.
Immune chemicals near a B cell activate a specific switch region to tell it what kind of antibody to produce. The selected switch region produces an RNA strand that affixes itself to the DNA that spawned it, the investigators found. “It tends to stick with the DNA instead of falling off like normal RNA,” says Lieber.
In a manner that remains unclear, this RNA-DNA structure marks the selected gene, which then remains when a DNA-cutting enzyme removes all the other stem-encoding genes. The result is a final blueprint for a tissue-specific antibody.
This is the first time that scientists have seen such RNA-DNA structures, although Lieber suspects some viruses create similar ones when they infect cells. His group continues to look for the DNA-cutting enzyme that participates in the recombination. Lieber speculates that a fuller understanding of the process may help thwart Burkitt’s lymphoma, a cancer of immune cells that occurs when class switch recombination goes awry.