Immunoglobulin M, or IgM for short, is the first class of antibodies to appear in response to exposure to antigen. Increasingly, scientists are interested in IgMs as therapeutics, but growing them in mammalian cells at commercial scale is very challenging. Now researchers find they can synthesize IgM in plants, according to findings detailed in the Proceedings of the National Academy of Sciences.
IgM is by far the physically largest antibody in the human circulatory system, and it ranks among the most complex of human proteins — for instance, they are each made up of 21 to 24 polypeptides. Complicating the matter further is how roughly 10 percent of each IgM’s weight is made up of complex sugar-containing structures known as N-glycans, and improper addition of these molecules could impair antibody function.
Molecular biologist Herta Steinkellner at the University of Natural Resources and Applied Life Sciences in Vienna and her colleagues noted that plants have correctly assembled mammalian proteins such as immunoglobulin Gs before. They sought to see whether plants could also correctly fold and assemble complex IgM.
The scientists introduced the genes to produce the cancer-fighting IgM PAT-SM6 in a close relative of tobacco known as Nicotiana benthamiana. The anti-tumor IgM accumulated in the leaves of the plants and assembled itself correctly.
“I was surprised that plants can make such complex human proteins like IgMs,” Steinkellner says.
Analysis revealed the N-glycans were attached onto the plant-derived IgMs in a pattern resembling those seen on human-derived IgMs. The plant-derived IgMs behaved virtually identically to human-derived IgMs when it came to binding onto human lung cancer cells on lab dishes.
The researchers suggest their work opens the door for commercial production of similarly complex proteins for pharmaceutical use. They note that future research using their system can investigate the role glycosylation has on the activity of antibodies and other vital proteins.