The Centenary Institute has made an important contribution to a significant study that suggests how infections can trigger serious autoimmune diseases such as rheumatic fever.
The research, just published in the international journal Immunity, shows how, in unusual circumstances, the B cells of the immune system occasionally work against the body, producing antibodies that attack the cells of our own organs—in the case of rheumatic fever, the heart.
The work was led by Associate Professor Robert Brink of the Garvan Institute, formerly a researcher at Centenary. And one of the important analytical techniques A/Prof Brink used to pursue his studies was developed by Centenary researcher, Dr Chris Jolly, who works on DNA repair in the Immune Imaging research program.
B cells are the components of the immune system that produce antibodies, the proteins that bind to and destroy invaders—such as viruses, bacteria or toxins—that the body wants to get rid of. The production of antibodies is stimulated by marker compounds—antibody generators or antigens—that are carried on the surface of the invader.
Antibodies capable of attacking and binding to antigens on the cells of our own body, self-antigens, can be disastrous. That is what occurs in devastating autoimmune diseases, such as lupus or rheumatoid arthritis. To prevent this from happening, the B cells are educated to tolerate the self-antigens around them as they develop and mature.
But when the body is infected by a disease-causing organism, the B cells go into overdrive producing a vast range of different antibodies in an attempt to find one that can take the invader out. It’s not surprising that sometimes the mechanism that generates all the different antibodies comes up with one that will bind to a self-antigen. Typically, the body deletes B cells making autoimmune antibodies before they can cause trouble. But in certain circumstances, it doesn’t. And that was the focus of the recently released study.
By keeping tabs on individual antibody-producing B cells in special transgenic mice as they responded to infection, Robert Brink and his team found that if an antibody to a common and widespread self-antigen emerged, the immune system would shut its production down. But if the self-antigen were rare or confined to a particular part of the body, such as the heart in the case of rheumatic fever, then the problem could pass under the radar, and an autoimmune disease could be triggered.