Researchers find more effective method of destroying B cells to treat autoimmune diseases

B cells protect the body from infections. But sometimes they misfire and cause serious illnesses. Researchers at the University of Connecticut have now shown that a single protein could be able to defuse degenerated B cells. Their results were published in the journal “The Journal of the University of Connecticut”. eBioMedicine.

B cells are immune cells that produce antibodies, proteins that capture foreign invaders and mark them for destruction. B cells are created in the bone marrow and then spread throughout the body, gaining experience in dealing with viruses, bacteria and other harmful influences. When a B cell is presented with part of an invader, it copies it and then produces antibodies to fight it.

Sometimes, however, B cells get confused and start making antibodies against the body’s own cells instead. This can lead to autoimmune diseases such as multiple sclerosis or lupus. B cells can also be involved in cancers such as lymphoma.

Certain treatments for lymphoma, lupus, multiple sclerosis, and other B-cell diseases aim to rid the body of the B cells that are causing the damage. For some people, these treatments can be very effective. But not for all people; sometimes the treatments make the disease worse. And sometimes the treatments work for a short time, but when they are stopped, the symptoms flare up again.

Penghua Wang, an immunologist at the UConn School of Medicine, was working on something very different when he came across a much more effective way to destroy 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.

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

Wang and his colleagues tried to breed mice that developed normal immune systems in infancy, then blocked Ubxn3b when the mice became 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 without Ubxn3b were otherwise normal and fairly healthy.

“The rest of the immune system looked good in these Ubxn3b knockout mice,” says Wang. “This gene function in cell survival is very specific to B cells.”

The researchers are now looking for partners to study animal models of multiple sclerosis or other autoimmune diseases to test whether blocking Ubxn3b could actually be therapeutic. They also plan to develop a detailed molecular mechanism that explains how the gene regulates B cell survival.