A group of scientists has identified genes linked to high production of a key antibody, which has the potential to advance manufacturing of antibody-based therapies for diseases such as cancer and arthritis.
A collaboration led by University of California-Los Angeles and the Seattle Children’s Research Institute yielded new knowledge about the genes responsible for the production and release of immunoglobulin G, the most common type of antibody in the human body.
Immunoglobulin G, or IgG, stores memories of past infections and tags dangerous microbes to be eliminated by immune cells. Mothers’ IgG is also vital for their newborns’ immune defense.
Scientists have known for decades that a population of white blood cells, called plasma B cells, make IgG. But the molecular mechanisms that enable plasma cells to secrete antibodies into the bloodstream are still not fully understood.
In order to learn more about those mechanisms, the researchers captured thousands of single plasma B cells as well as their individual secretions, and then connected the amount of proteins each individual cell released to an atlas mapping tens of thousands of genes expressed by that same cell.
To collect the cells and their secretions, the researchers used microscopic, bowl-shaped hydrogel containers called nanovials, which were developed in prior UCLA research.
Their analysis, detailed in the journal Nature Communications, found that genes involved with producing energy and eliminating abnormal proteins were even more important for high IgG secretion than the genes containing instructions for making the antibody itself.
They also discovered that the presence of CD59, a gene that had not previously been linked to IgG secretion, is a better predictor of high-producing plasma cells than other genetic markers already associated with this cell type.
“These processes in cells are like an assembly line for making proteins, and there are lots of places where you could see bottlenecks,” said Dino Di Carlo from UCLA’s Samueli School of Engineering and a co-corresponding author of the study.
“If a cell is making a lot of proteins, it’s using a lot of energy and needs a way to correct the proteins that get messed up.”
Knowing which genes are associated with higher secretion of an antibody could be used by pharmaceutical makers to engineer cells that secrete large volumes of the antibody.
That knowledge could also be applied to an emerging strategy that introduces engineered cells directly to patients’ bodies, such as the potential cell therapies under development by University of Washington immunologist Richard James, a co-corresponding author of the paper.
In future studies, the researchers hope to identify all of the genes that affect plasma cells’ production and secretion of IgG.
