Clues Could Prove That Antibodies Are Fine-Tuned To Fight Infection

Clues Could Prove That Antibodies Are Fine-Tuned To Fight Infection ...

Researchers at the University of Alberta have discovered new information about a cell structure in the immune system that is fundamental in helping individuals improve their abilities.

The antibodies our immune system produces need to be refined in order to achieve maximum effectiveness. When a vaccine or pathogen is first introduced into our bodies, antibodies produced against these agents help us protect but they should be optimized, according to Matthew Macauley, an assistant professor at the Department of Chemistry.

Slowly, our immune system improves the ability of the antibody to recognize their target, and improves them.

Mutations in a pseudo-random manner make antibodies more adaptable to their target in a process called antibody affinity maturation. Finally, mutations in a highly orchestrated series of events select antibodies.

Getting to the centre of how antibodies adapt

In the germinal centre, a complex process of choosing the best antibody occurs. According to Jhon Enterina, the scientist who was the first author of the study, believes that science must understand this important location and the process of development.

Immunologists have used this technique to research the germinal centre for the past 20 to 30 years, primarily to identify specific carbohydrates on the surface of the white blood cells in the germinal centre. Macauley, whose research as a network investigator with the pan-Canadian research network GlycoNet focuses on carbohydrates, took notice of this.

When we arrived at the realization that these carbohydrates have a function, we found out why. They are probably not just there for us to identify, but they are likely to play an important role.

B cells are the type of white blood cell that makes antibodies. When B cells recognize a component of a vaccine or pathogen, they convert them into more advanced germinal centre B cells. This are the specialized cells that have a unique set of carbohydrates on their surface. Thats where Macauley saw an opportunity to get to the bottom of the process.

As the carbohydrates evolve in the germinal center into a different type, we developed a somewhat straightforward method to test for their function: to stop them from changing and see what happens.

Macauley and his team developed a specific model to help prevent these changes from occurring. This was done at the genetic level. Normally an enzyme is turned off in germinal centre B cells, therefore we simply didn''t allow them to turn it off.

They discovered key information about the germinal structures that will be implemented in the system.

These changes were linked to a protein receptor called CD22, which recognizes the key carbohydrates.

The germinal centre is particularly challenging to study because it can''t be used in a petri dish. Upon receiving germinal centre cells outside of their natural environment in the body, they die within a few hours. Moreover, the cells within the germinal centre divide at the fastest rate of all mammalian cells, even faster than cancer cells.

The reason these cells divide so quickly is that it''s essential for our bodies to develop antibodies as quickly as possible to neutralize pathogens before it''s too late, according to Macauley.

Many illnesses, such as cancer or autoimmune illnesses, have resulted in the germinal centre becoming out of control. However, before scientists can determine how to control this key area in the body, we must understand what appropriate controls are in the first place, and there is still a long way from having all the answers.

It''s a difficult process, and despite all of the insights that have been published in the last ten years, there are still many questions about the germinal center, therefore this is revealing another aspect of one of the mechanisms that controls it.

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