An entirely new form of immune response has been described in the lamprey, an eel-like fish from an ancient lineage. This discovery casts a class of immune cells in a new light and raises the possibility that there is more to the immune system of higher vertebrates than has been realized.
The sea lamprey Petromyzon marinus is one of only a handful of species descended directly from primitive vertebrates that undulated through the ancient oceans more than 400 million years ago. Such evolutionary relics are thought to offer a glimpse of what vertebrates were like at a time when jaws and paired fins had yet to evolve. Studies of the lamprey's immune system in the 1960s and '70s revealed that it has some degree of adaptive immunity, tailoring its immune response to fend off pathogens it has never encountered. However, lampreys don't seem to be armed with antibodies and T cell receptors--the conventional molecular tools that all jawed vertebrates including humans use to fight off novel pathogens. This suggests that lampreys have a completely different means of achieving adaptive immunity, but the details have remained a mystery until now, says Zeev Pancer, an immunologist at the University of Alabama at Birmingham.
To trigger the lamprey immune system, Pancer injected a cocktail that included Escherichia coli bacteria, sheep red blood cells, and pokeweed mitogen (among other things) into lamprey larvae. In most vertebrates, immune cells called lymphocytes are alerted to such antigens and then orchestrate the adaptive immune response, sending out tailor-made antibodies and T cells to seek and destroy the foreign material. The lamprey is different because its lymphocytes do not delegate responsibility but become active themselves and target the pathogen directly, says Pancer. The lymphocytes respond to the antigen cocktail by cranking out surface proteins called variable lymphocyte receptors, he and his colleagues report in the 8 July issue of Nature. These previously unknown proteins have a highly variable middle section that can be rearranged to customize an immune response to specific antigens, says Pancer.
This is a major advance in understanding the evolution of the vertebrate immune system, says Gary Litman, a geneticist at the All Children's Hospital in St. Petersburg, Florida. It also raises the intriguing possibility that similar mechanisms of lymphocyte-led adaptive immunity will be found in other vertebrates, says Jonathan Rast, a cell biologist at Sunnybrook and Women's College Health Sciences Centre in Toronto. "It now becomes much more plausible that this type of phenomenon is a widespread feature of immunity," he says.