Using sophisticated gene sequencing and computing techniques, researchers at Vanderbilt University Medical Center (VUMC) and the San Diego Supercomputer Center have achieved a first-of-its-kind glimpse into how the body's immune system gears up to fight off infection.
Their findings, published last month in the journal Nature, could aid development of "rational vaccine design," as well as improve detection, treatment and prevention of autoimmune diseases, infectious diseases, and cancer.
The study focused on antibody-producing white blood cells called B cells. These cells bear Y-shaped receptors that, like microscopic antenna, can detect an enormous range of germs and other foreign invaders. They do this by randomly selecting and joining together unique sequences of nucleotides known as receptor "clonotypes." In this way a small number of genes can lead to an incredible diversity of receptors, allowing the immune system to recognize almost any new pathogen.
Understanding exactly how this process works has been daunting. "Prior to the current era, people assumed it would be impossible to do such a project because the immune system is theoretically so large," said James Crowe Jr., MD, director of the Vanderbilt Vaccine Center and the paper's senior author. "This new paper shows it is possible to define a large portion," Crowe said, "because the size of each person's B cell receptor repertoire is unexpectedly small."
The researchers isolated white blood cells from three adults, and then cloned and sequenced up to 40 billion B cells to determine their clonotypes. They also sequenced the B-cell receptors from umbilical cord blood from three infants. This depth of sequencing had never been achieved before. What they found was a surprisingly high frequency of shared clonotypes. "The overlap in antibody sequences in between individuals was unexpectedly high," Crowe explained, "even showing some identical antibody sequences between adults and babies at the time of birth."
Understanding this commonality is key to identifying antibodies that can be targets for vaccines and treatments that work more universally across populations.