A team of scientists from Boston Children’s Hospital and Harvard University School of Medicine (USA) has identified – thanks to experiments with mice – a chain reaction that explains why our own bodies can turn against cells healthy. This discovery could transform our understanding of autoimmune diseases and how we treat them.
What is the trigger?
The reaction, discovered after four years of research in mice, has been described as a “runaway train” where a mistake leads the body to develop a very efficient way of attacking itself.
The study focused on B cells (because B lymphocytes play an important role in regulating the immune system, both under physiological and pathological conditions). These cells normally produce antibodies and program immune cells to attack unwanted antigens (or foreign substances), but experts found a “kill switch” in rodent B cells that distorted this behavior and caused autoimmune attacks.
According to one of the authors of the work, Michael Carroll, “once the body’s tolerance to its own tissues is lost, the chain reaction is like a runaway train. The immune response against the body’s own proteins, or antigens , it looks exactly as if the organism is responding to a foreign pathogen. “
These B cells could in turn explain the biological phenomenon known as an epitope (portion of a macromolecule that is recognized by the immune system) where our bodies begin to hunt down various antigens that should not be on the immune system’s “cleaning / hunting list. “.
The diffusion of epitopes in the body has been observed for a long time in the laboratory, but scientists did not know how it happened and why autoimmune diseases evolve over time to address an ever-expanding catalog of healthy organs and tissues.
So the researchers examined a mouse model with the autoimmune disease lupus, considered a “classic” form of autoimmune disease on which many others are based.
“ Lupus is known as the great mimic , because the disease can have so many different clinical presentations that it resembles other common conditions. It is a disease of multiple affected organs and with a plethora of potential antigenic targets,” comments Søren Degn, co-author of the job.
The scientists used fluorescent marker proteins to track different B cells in the rodents’ bodies. When B cells detect a foreign body – or something healthy that appears to be a foreign body – they move in groups called germ centers (this is why lymph nodes swell when we have a cold, for example).
B-cell clones fight each other within these centers so that the body can determine which antibody is best suited to combat the threat, and in the case of this study, it meant that one color ‘won out’ against the others.
The problem arises when the body incorrectly identifies a normal protein as a threat. When that happens, autoantibodies are produced that are very effective in damaging our own bodies.
The researchers have found that “over time, the B cells that initially produce the autoantibodies begin to recruit other B cells to produce additional harmful autoantibodies ,” says Degn.
So far this has only been seen in mice, but the researchers want to use this ‘confetti’ technique to see how this autoantibody B cell production is regulated and accelerated.
The blockage of the germ centers could be a break in the vicious cycle that autoimmune diseases create by effectively blocking the short-term memory of the immune system.
“This finding came as a surprise. Not only does it tell us that autoreactive B cells are competing within the germ centers to engineer an autoantibody, but we also saw that the immune response is amplified to attack other tissues in the body , leading to the epitope spreads at the speed of a runaway train, “Carroll clarifies.
Reference: Søren E. Degn, Cees E. van der Poel, Daniel J. Firl, Burcu Ayoglu, Fahd A. Al Qureshah. Clonal Evolution of Autoreactive Germinal Centers. Cell. 2017. DOI: http://dx.doi.org/10.1016/j.cell.2017.07.026
