B Cells Counter Inflammation By Releasing Acetylcholine

Researchers at Massachusetts General Hospital have published new research that is providing insights into the pathways that increase or decrease bone marrow’s output of white blood cells—including a surprising source of a neurotransmitter that protects the heart and arteries from inflammation.  The findings may lead to new treatments for conditions that arise when the balance of white blood cell production goes awry.

The nervous system plays a role in regulating blood cell production using neurotransmitters. “This is for instance important in people exposed to stress, where stress hormones—part of the ‘fight-or-flight’ response controlled by the sympathetic nervous system—may increase bone marrow activity and cardiovascular inflammation in response to the neurotransmitter noradrenaline,” says senior author Matthias Nahrendorf, MD, PhD, an investigator in MGH Center for Systems Biology and The Richard Moerschner professor at the MGH Research Institute and Harvard Medical School.

The parasympathetic nervous system have a counterbalance to this fight-or-flight reflex: neurotransmitter acetylcholine, which slows down responses and helps calm the body. Because acetylcholine can also have a protective effect against inflammation and heart disease, the MGH researchers set out to study this neurotransmitter in bone marrow. 

“When we looked into how acetylcholine acts on the production of blood cells, we found that it does the expected—it reduces white blood cells, as opposed to noradrenaline, which increases them,” says Nahrendorf. “What was unexpected though was the source of the neurotransmitter acetylcholine.”

The team found no evidence in the bone marrow of the typical nerve fibers that are known to release acetylcholine. Instead, B cells, which are themselves a type of white blood cell (most known for making antibodies), supplied the acetylcholine in the bone marrow. “Thus, B cells counter inflammation—even in the heart and the arteries—via dampening white blood cell production in the bone marrow. Surprisingly, they use a neurotransmitter to do so,” says Nahrendorf.

Tapping into this process may help investigators develop strategies to block inflammation in cardiovascular conditions such as atherosclerosis. “Ultimately this may lead to new therapeutics that combat myocardial infarction, stroke, and heart failure,” says Nahrendorf.

The findings were published in a recent issue of Nature Immunology.