LRI-Funded Researchers Discover How “Trojan Horse” B Cells Might Lead Autoimmune Attack

In the mythological tale, the Greeks were able to vanquish the city of Troy by infiltrating the city’s walls with a wooden horse hiding soldiers armed for attack. How dearly the Trojans paid for unwittingly opening the door to their foe! In lupus, the body might similarly mistake its enemy, according to findings just published in the September 15 issue of Journal of Immunology.

Researchers at University of Tennessee Health Science Center (UTHSC) in Memphis have discovered that certain B cells that appear harmless can in fact carry a potentially dangerous chemical cargo of immune complexes — large chemical networks connecting antibodies with antigens — which can get stuck in tissues, causing inflammation and organ damage. In lupus, immune complexes of autoantibodies and antigens are known to particularly damage the kidneys.

An Exception to the Rule

Dr. Marko Radic

Current understanding of immune complexes suggests that they form after the antibodies have been released from B cells, the cells involved in making antibodies. However, Dr. Marko Radic and his colleagues have revealed an unexpected exception to this accepted pathway.

The researchers had previously observed that while some potentially dangerous, self-reactive B cells go through a process that should render them harmless, they can continue to produce antibodies that react against the body’s own cells. It was further determined that the antibody produced by these B cells accumulates inside the cells in the Golgi apparatus, a part of the cell considered the distribution and shipping center for its secreted products. Not only did the antibodies accumulate in the Golgi, but they also formed large, round immune complexes that were eventually ejected from the cells. Because of their shape, the team named these complexes “spherons.”

“We consider B cells that produce spherons as “Trojan Horses” because they may arise in a normally functioning immune system and appear as innocuous cells,” explained Dr. Radic. “However, once activated, they may release their pre-formed immune complexes that could go on and cause tissue damage.”

The researchers’ next steps will be to find out whether spherons are produced in mice with lupus and if they cause kidney damage. These discoveries are the outgrowth of investments LRI made in the work of Dr. Radic and his colleague Dr. Salar Khan at UTHSC as well as a research consortium with Dr. Martin Weigert at University of Chicago and Dr. Jason Zhang at the University of Nebraska.

“We invested in this research to help uncover underlying mechanisms involved in the disease,” said Margaret Dowd, LRI President. “Dr. Radic’s discovery gives us an entirely new and unanticipated direction to explore in the search for new lupus treatments.”