Dr. Torres and Cristina L. Swanson PhD, a postdoctoral fellow in his lab, studied a process that contains elements of both innate and adaptive immunity, known as the T-cell independent antibody response. While B cells are most widely recognized for their contributions to the adaptive immune response, some begin producing antibodies soon after an infection begins. Instead of detecting a single specific protein associated with the invader, they detect repetitive molecules linked together, such as those found in a bacterial cell wall or viral capsid.
This process has been studied for many years using synthetic molecules as model antigens. Drs. Torres Swanson thought that experiments using just the synthetic antigens did not accurately reflect what occurs in the real world. They reasoned that B cells would almost never encounter a bacterial cell wall or viral capsid alone; an intact cell wall would almost always also contain other molecules that activate the innate immune response as well. So the researchers decided to inject mice with the synthetic antigen plus a molecule that binds an innate receptor, known as TLR ligand. Dr. Swanson performed the majority of the experiments as part of her doctoral thesis work.
The results were striking. Early antibody levels doubled when the TLR ligand was added. The mix of antibodies shifted as well, from 61 percent IgM to 82 percent IgG, which is a highly effective weapon against disease-causing organisms. The IgG levels remained elevated in mice for 182 days, as long as the researchers measured them. The long-lived persistence of this effective antibody suggests that the observations could be adapted to make more effective vaccines.
The researchers found that the TLR ligand spurred other cells to release type I interferon. That, in turn, activated follicular B cells to release the IgG antibodies. Prior to that, scientists had believed that follicular B cells partic
|Contact: William Allstetter|
National Jewish Health