For virtually every invading pathogen, be it a bacterium, virus or another microorganism, the body has a unique antibody specially designed to stop it in its tracks. Made and released by a special type of white blood cell, B lymphocytes, antibodies search for and bind to a distinctive molecule located on the assigned invader, sending out a distress signal calling for other components of the immune system to seek out and destroy it.
Since the 1950s, scientists such as Nils Jerne and MacFarlane Burnet had proposed that we are born armed with a complete set of antibodies, even before we encounter an assault. But how the body with only tens of thousands of genes can generate the millions of antibody proteins needed remained a mystery, until Susumu Tonegawa revealed the elegant answer. Looking at immune cells from mice, he discovered that genes coding for antibodies were noticeably farther apart from one another on chromosomes belonging to embryos than those from adults.
Somehow these genes had been rearranged as these cells matured to become antibody-producing B lymphocytes. Investigating the genetic material in greater detail, Tonegawa found that rearrangement occurred because the genes that encode each of the different structural components of an antibody protein do not exist as individual, complete elements, but instead are made up of a string of several units. As each B lymphocyte cell is created during embryonic development, a unit within each gene is selected at random, and these are shuffled together to eventually form the final antibody product. In this way a huge number of possible combinations can be generated from a relatively small number of genes.
Uncovering this mechanism for antibody diversity revealed that genes are not fixed, they can rearrange within the life of an individual. Tonegawa likened this process to the manufacture of cars. An automobile company produces different models for different customers’ tastes, not by creating new pieces every time for each model, but by taking the same parts and assembling them in different configurations.
This Speed read is an element of the multimedia production “Immune Responses”. “Immune Responses” is a part of the AstraZeneca Nobel Medicine Initiative.
Their work and discoveries range from cancer therapy and laser physics to developing proteins that can solve humankind’s chemical problems. The work of the 2018 Nobel Laureates also included combating war crimes, as well as integrating innovation and climate with economic growth. Find out more.