When I was 19, I was a model for the “dress and suit” class at Rud Vocational School. The students had to learn how to sew a suit. I chose bottle green wool for a jacket with rounded edges and a pleated skirt. It was based on a standard pattern, and I tried on the suit several times along the way to ensure it would fit my body perfectly. This is exactly the case with our antibodies as well.
Few genes, many combinations
The B-cells of the immune system produce antibodies against invading microbes. Antibodies are made by combining a few specific gene motifs in many different ways. They are made following the same pattern, although there are variations in the specific design of each individual antibody. Just like how I got a suit with the possibility for variation within a given framework.
The first time a microbe binds to the B-cell receptor, the receptor usually does not fit perfectly with the microbe. However, the B cell will still be stimulated to divide and start producing antibodies, i.e. receptors that can be released from the cell into the blood.
Random changes
A B cell that is stimulated to divide will first become two cells, then four, eight, and so on. These daughter cells will also have B-cell receptors that can bind to microbes.
However, in the daughter cells, random changes will occur in the B-cell receptor gene. As a result, all the daughter cells will have B-cell receptors that are slightly different from the original B cell. This phenomenon is called “somatic hypermutation“. It is similar to the times when I tried on the suit before it was finished, with small changes being made each time.
Darwin in the body
As long as the microbe is present, the new B cells will also bind to the microbe. If the altered receptor fits the microbe better, the B cell will receive a signal to continue dividing.
If, on the other hand, the receptor is a poorer fit, the B cell will not receive any signal and will soon be outcompeted by B cells with receptors that are better suited to the microbe. This is Darwinian evolution.
In this way, antibodies against a microbe become a combination of ready-to-wear and tailoring.
Repeated adjustment when needed
I still have the bottle green suit. After more than forty years, it still fits, if no longer perfectly. Although I weigh the same as before, the jacket has clearly become tighter around the shoulders. The body has simply changed a bit. Unfortunately, there is nothing I can do about my body, and I am unlikely to make any adjustments to the suit either.
For B cells, it’s different. After the initial encounter with a microbe, some B cells with receptors tailored for that microbe will remain in the body for several decades.
During the next encounter with the microbe, perhaps many years later, the microbe might have changed a bit, becoming slightly “broader around the shoulders.” In that case, the B cells will be stimulated again to divide and activate the “change machinery” for their B cell receptors.
And unlike my bottle green tailored suit that can no longer be altered, we will once again have antibodies that fit perfectly to the microbe as it is right here and now.
Blog post by Anne Spurkland, first published in Norwegian in 28 October 2012, translated to English 23 January 2024.
ImmuneGlimpse 