Immunity; how B cells make antibodies (Introduction)

by David Turell , Thursday, September 14, 2017, 18:51 (2410 days ago) @ David Turell

By first damaging or changing their DNA to make specific antibodies against specific infections:

https://www.sciencedaily.com/releases/2017/09/170913084427.htm

"In response to infection the immune system produces unique antibodies to target each illness. To make these new antibodies, cells in the immune system must intentionally damage their own genes, meaning they run the risk of becoming cancer cells. New research reveals how a proteins called Tia1 acts as a hair-trigger for DNA repair, allowing the immune system to walk the line between health and harm.

"To fight infections cells in the immune system play a dangerous game with their own genes. Damaging genes allows B cells to make antibodies that are specifically equipped to target to specific causes of illness, but damaging genes also puts them at risk of becoming cancerous.

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"All cells experience DNA damage but it's usually minor and can be repaired. The latest research, published in the journal Nature Communications, highlights that standard repair processes are too slow for B cells, where intentional DNA damage is more severe. The results show that B cells plan ahead, priming the DNA repair process early, so when they intentionally damage their own DNA it can be fixed before it causes lasting harm.

"As the paper's first author, Dr Manuel Díaz-Muñoz said: "B cells walk a fine line, some DNA damage is needed for them to make effective antibodies to fight infections, but too much and they become harmful. It's a tough situation to manage biochemically. Tia1 controls the production of a number of proteins that help cells respond to damaged DNA. Tia1 allows a rapid response from B cells so they can repair DNA damage at a moment's notice."

"Each illness requires a specific antibody to defeat it. By damaging and repairing the genetic instructions that make antibodies, each B cell produces a unique antibody type and the most effective ones are then used to fight disease. This causes extensive damage to the DNA inside B cells and must be rapidly repaired or genetic mistakes may weaken the immune system or even cause cancer.

"Scientists believed that B cells only turn on DNA repair genes when they are needed to repair damage. Yet, these new results completely change this view. These genes are constantly active, but cells only use the information in these genes to make proteins when there is a lot of DNA damage. B cells prepare templates for the proteins but don't go on to make the proteins themselves.

"Tia1 is the protein that enables B cells to stop making DNA repair proteins part way through. When DNA damage is low, Tia1 gathers together the protein templates, called mRNAs, for lots of different DNA repair proteins. When DNA damage increases Tia1 can quickly release all the mRNAs it collected and the cell uses them to make lots of the proteins it needs to fix its genes.

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"'Remarkably, our data suggest that regulation of mRNAs by Tia1 rather than protein destruction controls DNA repair in activated B cells. This is an attractive and little explored mechanism that we are now starting to understand. Controlling protein production in this way is important in other healthy and diseased cells and it will be interesting to see if a similar system exists in other places.'"

Comment: Since infections can always occur without warning, this hair-trigger system must have been designed intact from the beginning. It could not be built bit by bit. Specifically out of billions of different proteins, how did evolution find Tia1 to do the job without guidance?