Scientists Discover How/When Infection Triggers Autoimmune Disorders

A team of researchers at the Garvan Institute of Medical Research in Sydney, Australia, have identified a weak link in the immune system and “the exact conditions under which an infection can trigger an autoantibody response.” According to the researchers who specialize in the study of how immune B cells produce self-attacking rogue antibodies, their finding “explains a lot about how autoimmune conditions that target particular organs such as the heart or nervous system could develop after an infection.”

Immune cells go through processes when they are first formed that ensure they are able to identify self and, therefore, avoid self-attack. But the antibody-creating B cells go through a second phase of development when the body is engaged in trying to fend off disease or infection. To cope with the immeasurable range of microbes in our environment, B cells have evolved the ability to mutate their antibody genes randomly until they produce one that sticks strongly to the invader. At that point, the successful B cells proliferate and flood the system with these new antibodies. This “high affinity antibody” generation process occurs rapidly within specialized environments in the lymph system known as germinal centers. Most of the time, germinal centers help fight disease and build up a protective armory for the future. But the urgency and speed at which B cells mutate within the germinal center, as well as the random nature of the process, sometimes creates an antibody that also happens to match self and has the potential to cause autoimmune activity.

The researchers, who developed sophisticated mouse models to investigate when and how this happens, found that when the invading antigen is abundant and generally present throughout the body, rogue autoantibody-generating B cells are deleted and autoimmunity is avoided. But when the target antigen is located only in a tissue or organ remote from the germinal center, B cells capable of reacting against both antigen and self are able to escape the germinal center and produce autoantibodies. Essentially, the researchers say they’ve shown there’s a hole in self-tolerance when it comes to cross-reactive autoantibodies that can attack organ-specific targets. Their findings suggest that if enough is known about the disease and the molecular messaging systems involved, it may be possible in the future to modulate the germinal center response. They plan to continue to use their new mouse model to study the various molecular reactions involved in the progression of an autoimmune response.

The study was published in the November 8 edition of the journal Immunity.