New perspective on how immune cells perceive viruses and other threats

A textbook chapter on the immune system may need to be revised as a result of a new study from Aarhus University.

The study, published in the journal Nature Communications, reveals important new information on B cells, which are an important component of the body’s defense system.

B cells are the cells that make protective antibodies when people are vaccinated or infected, but they are also the cells that produce harmful antibodies in the case of allergies or autoimmune diseases.

The researchers analyzed the initial phase in activating B cells, namely the activation process that occurs when the lymphocytes recognize a specific target or “enemy”—an antigen.

Method

The researchers used an interdisciplinary strategy that included two highly advanced, genetically modified mouse strains, a unique nanoscaffold made of modified nucleic acids, and a ground-breaking super-resolution microscopy method called DNA PAINT.

Previously, it was believed that the antigens from, for example, viruses or vaccines would have to cross-bind a B-cell’s receptors on the cell surface (see illustration). That is what it says in all the textbooks. But now we have shown that even antigens that can only bind one receptor at a time are able to activate the B cells.”

Søren Degn, Study Senior Author and Associate Professor, Department of Biomedicine, Aarhus University

He believed that the discovery is significant on several levels.

Degn further added, “The result is significant because it represents a breakthrough in our understanding of how these important immune cells ‘recognize’ their enemies. Once we understand what is going on, we can imitate it in the design of new vaccines, to ensure maximum effect. One might say that our findings can make us better at mimicking the pathogenic microorganisms, and thus better at provoking or ‘cheating’ the immune system into generating a good immune response when we vaccinate.”

A hotly debated topic in the field

The finding is intriguing because it provides fresh insight into the fundamentals of how receptors on the surface of cells transmit information within the cells, a crucial biological activity. This insight is relevant to both the study of immunology and cell biology in general.

Degn added, “The study enables us to better understand the background for one of the most important processes in the immune system, and one of the most important processes in cell biology. But it is clear that, in the long term, this could also have important application-oriented aspects.”

The researchers have begun preclinical vaccination trials with the objective of transforming their results into clinically viable vaccine designs. Researchers are also aiming to utilize the same tools in reverse to target and turn off detrimental immune system responses such as allergy reactions and autoimmune diseases.

“When we understand how the B cells are activated, we can create better vaccines. In the slightly longer term, we may also be able to switch off B-cell activation in cases where it is harmful. We are studying both of these in the CellPAT basic research Centre at Aarhus University,” Degn added.

For many years, experts have been debating the activation of B cells since the prevailing explanation for how immune recognition happens did not account for all of the observations.

In the current study, researchers from the Department of Biomedicine and iNANO in Aarhus have developed new tools that enable them to pierce the predominant model and therefore bury the decades-old paradigm in cross-disciplinary collaboration with the Max Planck Institute in Munich.

Degn concluded, “We have shown that the way in which the activation of B cells has been explained over the past thirty or forty years is wrong. This is an important finding because it opens the door to better vaccines and better treatment of a large group of diseases.”