Researchers Discover More Effective Way to Deplete B Cells for Treating Autoimmune Diseases

B cells protect your body from infection. But sometimes they fail and cause debilitating diseases. Researchers at the University of Connecticut have shown that a single protein may be able to defuse malfunctioning B cells. Their findings are published in the journal eBioMedicine.

B cells are immune cells that produce antibodies, proteins that attack foreign invaders and mark them for destruction. B cells are born in the bone marrow and then spread throughout the body, gaining experience against viruses, bacteria, and other malicious actors. When a piece of an invader is presented to a B cell, the B cell copies it and then makes antibodies to fight it.

But sometimes B cells get disrupted and start producing antibodies against friendly cells in the body. This can lead to autoimmune diseases like multiple sclerosis or lupus. B cells can also be involved in cancers like lymphoma.

Some treatments for lymphoma, lupus, multiple sclerosis, and other B-cell diseases try to eliminate the B cells that cause the damage. In some people, these treatments can be very effective. But not in everyone. Sometimes the treatments make the disease worse. Sometimes they work for a while, but when they are stopped, the symptoms return.

Penghua Wang, an immunologist at the UConn School of Medicine, was studying something completely different when he stumbled upon a much more efficient way to deplete B cells. Wang and his colleagues Tingting Gang and Duomeng Yang, both immunology researchers at the School of Medicine, were studying a protein called Ubxn3b and its role in COVID infection.

Mice lacking the Ubxn3b gene were known to be highly susceptible to respiratory viruses. They found that Ubxn3b was important for viral immunity in mice because it promoted the development of B cells. Mice lacking the Ubxn3b gene were almost entirely devoid of B cells.

Wang and his colleagues tried breeding mice that had developed normal immune systems as infants, then blocked Ubxn3b once the mice were adults. The mice stopped producing B cells in their bone marrow, and existing B cells in the spleen, lymph nodes, and other peripheral areas of the body died without the protein. The mice lacking Ubxn3b were normal and otherwise quite healthy.

“The rest of the immune system seemed fine,” Wang says of these mice lacking the Ubxn3b gene. “The function of this gene in cell survival is very specific to B cells.”

The researchers are now looking for partners who are studying animal models of multiple sclerosis or other animal models of autoimmune diseases to see if blocking Ubxn3b would actually be therapeutic. They also plan to develop a detailed molecular mechanism explaining how the gene regulates B cell survival.