R-Loop Controls Immunoglobulin Class-Switching

Researchers have found that a DNA/RNA hybrid known as an R-loop may control how and when the large immunoglobulin IgM is trimmed into the four smaller classes of immunoglobulins (IgA, IgG, IgD and IgE).

The size of an immunoglobulin is important because it determines where in the body the antibody can go. IgM is found predominantly in the bloodstream, while IgG can pass through the walls of capillaries and cross the placenta. IgA can be detected in the lungs, the digestive tract, and in various secretions (e.g. saliva, sweat, tears).

The current study, published April 7, 2003, in the online edition of Nature Immunology, is among the first to shed light on the process by which IgM is trimmed to form the other classes. "The way in which the five different immunoglobulin classes are created is a nearly perfect system,” explained senior author Dr. Michael Lieber, professor of pathology and biochemistry at the University of Southern California (Los Angeles, USA; www.usc.edu). "And yet, the DNA mechanism for how a cell switches from producing one class to producing another has remained a mystery for almost 20 years.”

The investigators found that a strand of RNA became bound to one strand of an unzipped DNA molecule to form an R-loop with a displaced guanine (G)-rich strand that was single-stranded. The R-loop acted as a marker, guiding enzymes to cut the DNA at the point above the loop. This is an unusual occurrence of enzymes recognizing DNA structure rather than the sequence of nucleotides that make up the molecule.

According to the authors, the discovery of the R-loop may shed light on the development of B-cell cancers such as myelomas. Should an error occur during the class-switching recombination event, it might cause activation of an oncogene.



Related Links:
University of Southern California