Protecting the Home Front

Our body is protected by valiant warriors – but even they were once defenseless. Take, for instance, newborn B cells (a type of immune cell). When they reach adulthood they are able to ward off some of the body's most formidable intruders; yet when young they are too vulnerable to perform such dangerous tasks. Nonetheless, the young cells must set out on a treacherous journey from the bone marrow (where they are created) to the spleen (where they mature). Throughout the journey they are kept out of harm’s way.

Their secret shield, found Dr. Idit Shachar of the Weizmann Institute’s Immunology Department, is a substance called interferon gamma. When secreted in minute quantities, it causes the young cells to sense where the danger is and quickly avoid it. This finding was surprising since the same substance had been known to do the opposite: When secreted by adult T cells (another type of immune cell), it effectively sets them on the warpath, leading them to the foreign intruders. The key, says Shachar, is quantity. Different quantities of the same substance result in opposite effects.

Once the young cells have reached the spleen, they begin to mature. Shachar found a molecule that controls this process. “Again, we had a lot of convincing to do,” she says, since the molecule was previously believed to act only as a chaperone to another molecule that had an important role in the immune system. “The fact that the ‘chaperone molecule’ was preserved throughout evolution [hence its name, ‘invariant chain’] hinted to us that it must itself be a major player in immune activity.”

Dr. Shachar’s research is supported by Mauricio Gerson, Mexico; Udi Angel, Israel; the Harry and Jeanette Weinberg Fund for Molecular Genetics of Cancer; the Weizmann Institute of Science-Yale University Exchange Program; the Philip M. Klutznick Fund; and the Arie and Ida Crown Memorial Charitable Fund. She is the incumbent of the Trudy and Alvin Levine Career Development Chair.