Researchers from the University of Pennsylvania School of Veterinary Medicine have discovered a unique evolutionary link between the immune systems of fish and mammals in the form of a primitive version of B cells, white blood cells of the immune system. Their studies link the evolution of the adaptive immune system in mammals, where B cells produce antibodies to fight infection, to the more primitive innate immunity in fish, where they found that B cells take part in phagocytosis (literally: cell eating), the process by which cells of the immune system ingest foreign particles and microbes.
The finding, which appears in the online version of Nature Immunology and will be featured on the cover of the October issue, represents a sizeable evolutionary step for the mammalian immune system and offers a potential new strategy for developing much-needed fish vaccines.
"When examining fish B cells we see them actively attacking and eating foreign bodies, which is a behavior that, according to the current dogma, just shouldn't happen in B cells," said J. Oriol Sunyer, a professor in Penn Vet's Department of Pathobiology. "I believe it is evidence for a very real connection between the most primitive forms of immunological defense, which has survived in fish, and the more advanced, adaptive immune response seen in humans and other mammals."
About 400 million years ago, the earliest ancestors of modern fish split off of the evolutionary pathway that became the earliest ancestors of modern mammals. In modern mammals, the B cell is a highly adapted part of the immune system chiefly responsible for, among other things, the creation of antibodies that tag foreign particles and microbes for destruction. Mammals have phagocytic cells, but they are a specialized few cells identified apart from the complex interactions that drive other white blood cells.
Sunyer and his colleagues discovered this previously unsuspected B cell activity while examining the immune cells of rainbow trout and catfish. The researchers determined that these attack B cells account for more than 30-40% of all immune cells in fish, while phagocytic cells only make up a small portion of the total number of immune cells in mammals. Further research also showed that a significant portion of amphibian B cells retained their digestive traits.
"The immune systems of amphibians and fish are far less advanced than ours," Sunyer said. "When you only have a rudimentary adaptive immune system, it helps to have more phagocytic cells to compensate, which is what has served fish so well over the last 400 million years."
In the past, research on the immune systems of more primitive species has paved the way to the discovery of new molecules and pathways that are critical to the immune response in humans and other mammals. B cells themselves, for example, were first discovered in chickens in the 1960s. According to Sunyer, the Penn findings are not only important for understanding the evolution and function of immune cells in fish but also may point out to novel roles of B cells in mammals.
At this point, we cannot rule out the possibility that small subpopulations of phagocytic B cells, perhaps remnants of those present in fish, are still present in mammals, Sunyer said.
Their findings also have an agricultural implication. The current vaccines given to farmed salmon, for example, appeal to the fish's adaptive immune response, which this research has now shown to be a smaller part of the overall fish immune system than previously thought.
"If we work to create vaccines that encourage phagocytic B cell to respond to infection, then we would play to the strengths of fish immunity," Sunyer said. "In the long term, farming is a better, more environmentally sound approach to fishing, so better vaccines may make the practice more financially attractive to fisherman and less destructive to fish populations."
There is little doubt that, despite the behavioral differences, the fish B cells represent a less advanced version of mammalian B cells. Sunyer found the very cellular structures that medical science has used to define B cells in humans to be present in fish B cells, which is why they are able to label them as B cells in the first place.
"Here we have a clear picture of where one part of the immune system, primitive phagocytes, adapted over time to serve a more complex role as part of the immune system that humans enjoy today, Sunyer said. There is still much we can learn about our own health through the ongoing study of immune system evolution among all organisms.
Funding for this research was provided by the National Science Foundation and United States Department of Agriculture.
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