Immune cells previously thought to be harmful, or at least useless, may hold the key to creating vaccines against diseases have traditionally been enigmatic.
A report, published in the April 2018 issue of Science, revealed that immune cells called lymphocytes may actually be able to fight infections that have been difficult to eradicate, such as HIV and campylobacter. These diseases hide from the immune system by mirroring our own cells, according to the report, but researchers found that these B-cells that were once believed to be "silenced" could actually be used as a kind of secret weapon.
Researchers have long speculated on the purpose of these lymphocytes, particularly when the human body has them in such large quantities, the report noted.
Deborah Burnett, BVSc, of the Garvan Institute of Medical Research in Australia and lead author of the report, said the report answers long-standing questions about the purpose and function of these immune cells. One known function of these cells was that, when activated, they could produce undesirable autoimmune reactions. But the report also revealed that these cells could actually be helpful.
"Since their discovery 30 years ago, the ongoing question has been ‘why does the body not simply delete these cells in the bone marrow, thereby avoiding the potential for them to become harmful cells later in life?’ In this study we have answered this conundrum," Burnett said. "These cells can be reactivated, mutate away from binding to your own tissues and become essential parts of an immune response against an invading threat. This knowledge may help patients with autoimmune disease come to terms with the nature of their disease and why it has occurred."
According to the report, researchers now suspect that the same process through which these cells produce antibodies that cause autoimmune reactions can also be used to program these cells against foreign infections.
"Until now these self-reactive B-cells were assumed to be the 'bad apples' of the immune system. Potentially dangerous cells that clog up the immune response without having any useful purpose", Burnett said. "We have now shown the opposite is true. These cells are not rare, they actually make up 50% of B cells in the periphery. We’re hoping that with this research clinicians will now start to consider that these cells can also be critical parts of an immune response a 'sleeper army' so to speak."
Pathogens are constantly in battle with our immune system, Burnett adds. They are constantly evolving and developing strategies to evade immune detection at the same time the immune system tries to develop new ways to fight them. A common strategy of some foreign bodies, such as HIV and influenza, is to mimic our body's own tissue, making the creation of effective vaccines difficult—until now.
"The self-reactive B cells we have explored in this study would be the perfect candidate target cells to make antibodies to these kinds of viruses. However until this point they have been almost completely ignored," Burnett said. "We hope that this research will now result in groups around the world focusing their effects on utilising these self-reactive B cells to produce vaccines to targets that closely mimic our own proteins, which until this point we have been unable to make vaccines for.
“As such, utilisation of vaccine strategies that target cells could result in additional preventative health measures for huge subsets of the population,” she added.
The research team used mouse models to study DNA mutations in the germinal centers where these cells are activated during an immune response. Researchers were able to intercept these cells in the germinal centers and reprogram then to stop binding to mouse tissues and instead increased their ability to bind to foreign bodies 5,000-fold. The hope is that this discovery could be used to develop new treatments or vaccines for diseases that have previously been able to hide from immune responses.
"This study opens the gateway for a flood of vaccine development strategies targeting these self-reactive cells," Burnett said. "We hope that the findings of our study will in the future result in range of new vaccines being available in clinical practice against pathogens which until this point were impossible to vaccinate against."