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New Discoveries about IgM and CD5L: Implications for Antibody Therapeutics

ENGINEERINGNET.BE – After a virus or bacteria enters our body, Immunoglobulin M (IgM) is the first antibody that the immune system produces.

IgM prevents infections by binding to a pathogen. The pathogen can then no longer enter a cell to spread.

IgM has been studied for decades in labs around the world. As early as the 1990s, it was thought that they had determined how the antibody is constructed: it is a large molecule shaped like a starfish with five arms.

This structure is described this way in all textbooks. Although it was already known that the protein CD5L can bind to IgM, the Dutch University of Utrecht and the Sanquin blood center have now shown for the first time that CD5L is bound to all IgM in the blood.

At the same time as the Utrecht scientists, researchers from Sanquin also discovered that something was wrong with the structure described in the textbooks. The two groups decided to join forces to find out exactly what was going on. They combined different techniques to do this.

UUtrecht determined the mass of IgM. For example, it was shown that a small protein was missing from the antibody’s structure. Sanquin developed methods to distinguish CD5L that is free in the blood and CD5L that is bound to IgM. The researchers also discovered that the concentrations of IgM and CD5L in the blood always rise and fall together.

According to Prof. Dr. Albert Heck of UUtrecht, the discovery raises many new questions. It is still unknown where CD5L is made and where it is linked to IgM. The function of the CD5L protein as part of IgM is also unclear.

Remarkably, IgM in saliva and milk is not bound to CD5L at all. Heck: “That can be a form of fine-tuning. Antibodies are locally adapted to the pathogens they most frequently encounter. There are different bacteria in your blood than in your mouth or on your skin.”

CD5L could also work as a kind of transport passport. “Perhaps IgM needs CD5L to enter the blood, or CD5L must be surrendered in order to pass from the blood into milk or saliva.”

The researchers involved are continuing their research into the formation and function of CD5L together. Heck: “These results put previous research on so-called free CD5L in a different light, so it may have to be interpreted differently.”

“Companies that now produce IgMs as therapeutic antibodies will also have to look carefully at whether they are making the right molecule. Depending on the precise role of CD5L, it may be possible to make IgMs that are specifically directed to the blood or specifically to the saliva goes.”

In the photo above: the five-armed IgM with the CD5L protein attached (red).

2023-12-07 15:24:30
#Important #antibody #blood #carries #surprise #Engineeringnet

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