Putting the "B" in Rheumatology

B-cells, a type of white blood cell, are one of the main components of the body’s immune defense system, which fights off infections and foreign bodies. In people with normal immune systems, B-cells help detect foreign antigens and produce antibodies to block them and render them harmless. But sometimes this defense system goes haywire, and instead of fighting foreign antigens, the body sends out a cascade of immune reactions against its own tissues. This overactive immune response can lead to autoimmune diseases such as vasculitis and lupus. The National Institutes of Health estimate that up to 23.5 million Americans suffer from some sort of autoimmune disease—and that the prevalence is rising.

Recently, scientists have learned that the role of B-cells in immune system regulation is more complex than they had previously thought. B-cells seem to be the ringleaders of the immune system, sending signals to activate the autoimmune response or tamp it down. When those signals get crossed in the immune system, resulting in autoimmune disease, B-cells are often to blame. Beyond producing antibodies, researchers are finding that B-cells have a broader range of mechanisms, including secreting proteins called cytokines that can cause inflammation, and stimulating T-cells, which are also white blood cells that attack invaders in the body. B-cells can also cause “apoptosis,” which is programmed cell destruction.

Because B-cells play such an important role in regulating the immune system, researchers in the last decade have turned to them as an area of research in the fight against autoimmune disease. Many approaches to depleting B-cells are being developed. Some work to induce negative signaling in B-cells, and others block B-cell survival and activation.

The more researchers have learned about B-cells, the more they realize that understanding the role of B-cells may help people with other diseases. With the expanded understanding that B-cells impact the proliferation of T-cells, researchers have studied B-cell depletion therapy to treat diseases that are mediated by T-cells, such as multiple sclerosis and type one diabetes.

Since B-cells play an important role in protecting the body, taking them out runs the risk of infection, so researchers have had to balance the risks and benefits. With life-threatening diseases, such as cancer, those benefits clearly outweigh the risks. One of the most exciting aspects of B-cell treatment is that it may be useful in patients who have rare diseases and no other treatment options.

For the most difficult to treat patients, with the most serious autoimmune diseases, B-cell depletion therapy may be a promising option.