New study challenges decades-long understanding of our immune system

Amazing stuff! With new methods and instruments come new discoveries! This could be a breakthrough!

"Method

The researchers applied an interdisciplinary approach, which encompassed, amongst other things, a ground-breaking super-resolution microscopy technique called DNA PAINT, as well as a unique nanoscaffold made of modified nucleic acids and two sophisticated, genetically modified mouse DNA strains."

"A recently published study from Aarhus University may mean a textbook chapter on the immune system will have to be rewritten.

In the study, published in the journal Nature Communications, the researchers reveal crucial new knowledge about B cells, which form a vital element in the body’s defence system. B cells are the cells that generate protective antibodies when we are vaccinated or have an infection – and it is also the B cells that produce harmful antibodies in connection with allergies or autoimmune diseases.

The researchers have examined the earliest step in activating the B cells, namely the activation mechanism that is triggered when the cells recognise a specific target or ‘enemy’ – an antigen.

“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’s 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,” ...

The discovery is important on several levels ...

“The result is significant because it represents a breakthrough in our understanding of how these important immune cells ‘recognise’ their enemies.  ...
The researchers have begun preclinical vaccine trials with the aim of translating the findings into clinically relevant vaccine design. They are also attempting to use the same tools in reverse, to target and turn off harmful immune system responses such as allergic reactions and autoimmune diseases. ..."

From the abstract:

"Antigen binding by B cell receptors (BCR) on cognate B cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution of BCRs is on the naïve B cell and how antigen binding triggers the first step in BCR signaling. Using DNA-PAINT super-resolution microscopy, we find that most BCRs are present as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20–30 nm. We leverage a Holliday junction nanoscaffold to engineer monodisperse model antigens with precision-controlled affinity and valency, and find that the antigen exerts agonistic effects on the BCR as a function of increasing affinity and avidity. Monovalent macromolecular antigens can activate the BCR at high concentrations, whereas micromolecular antigens cannot, demonstrating that antigen binding does not directly drive activation. Based on this, we propose a BCR activation model determined by the antigen footprint."

New study challenges decades-long understanding of our immune system

New study challenges our understanding of the immune system Researchers have created a radical new view of how immune cells recognise threats such as viruses. The discovery could be used to design better vaccines and to gain a deeper insight into autoimmune diseases and allergies.

Antigen footprint governs activation of the B cell receptor (open access)

Fig. 8: Schematic representation of central findings.