Ancient organism, modern immunity

The adaptive immune system, which can recognize, attack, and remember potentially harmful microbes, may have appeared on the evolutionary scene millions of years earlier than scientists thought. The immune system of the sea lamprey, a primitive, jawless fish, contains two cell types that recognize and respond to characteristic molecules associated with invading pathogens, researchers report in this week's __Nature__. "It's amazing to us," lead author linkurl:Max Cooper,;http://www.gra.org/EminentScholarsDetail/tabid/368/xmmid/1072/xmid/377/xmview/2/school/Emory%20University/Default.aspx an immunologist at Emory University in Atlanta, told __The Scientist__. "We never anticipated it."

The lamprey's imposing (but jawless) mouth
Image: US Environmental Protection Agency

Organisms such as plants and invertebrates have innate immune systems, which protect against pathogens in a nonspecific manner. More highly derived organisms such as mammals, however, also have adaptive immune systems, which can mount a two-pronged attack against foreign invaders. Adaptive immunity consists of humoral defenses, where B lymphocytes secrete antibodies against specific antigens, and cellular defenses, in which a host of T lymphocytes mediate a complex cellular attack. Scientists had previously identified cartilaginous fishes such as sharks, skates and rays as the most ancient possessors of this two-pronged adaptive immune system -- likely an evolutionary precursor to the mammalian adaptive immune system. The presence of adaptive immunity in lampreys, however, whose ancestors diverged from other vertebrates some 500 million years ago, means the general strategy is significantly older. Using a panel of monoclonal and polyclonal antibodies and challenges with bacterial antigens and human cells, Cooper and his team found that two lymphocyte types in lampreys had very different receptor repertoires and behaved similarly to the T and B cells of the mammalian adaptive immune system. Lampreys have one type of variable lymphocyte receptor (VLRA) that, like T cells, upregulates the expression of specific cytokine genes and inhibitory factors in response to antigens, and another receptor (VLRB) that, like B cells, binds native antigens and produces antibodies. VLRA and VLRB receptors were expressed by distinct lymphocyte populations, and the gene expression profiles for each type of cell resembled those of mammalian T and B cells. "The finding is amazingly interesting because either it shows that there's some kind of deep homology between these cell types or that there's some kind of convergent evolution," University of Toronto immunologist linkurl:Jonathan Rast,;http://medbio.utoronto.ca/faculty/rast.html who was not involved in the study, told __The Scientist__. "It's hard to know if the lampreys were the first jawless vertebrates to show this system," Brantley Herrin, Cooper's postdoc and coauthor on the paper, told __The Scientist__. He noted that Cooper's lab linkurl:reported;http://www.nature.com/ni/journal/v9/n3/abs/ni1562.html last year that the lamprey's VLRB cells behaved similarly to mammalian B cells. But the latest findings "suggest that there was an earlier division between humoral and cellular immunity than previously anticipated," Herrin said. The evolutionary rudiments of the human adaptive immune system could have first appeared in an even more ancient jawed fish whose existence has yet to be revealed in the fossil record, he added. Cooper noted that the lamprey system he and his colleagues described is likely an example of convergent evolution -- where distinct lineages evolve similar traits along distinct evolutionary paths -- rather than being an early version of the mammalian immune system. Rast agreed. "It's probably safer to treat [the lamprey VLR cells] as non-homologous until it's proven that they are," he said. Interestingly, lampreys lack a detectable spleen or thymus, which in jawed vertebrates serve as the sites for B cell and T cell maturation, respectively. Cooper said that his lab, in collaboration with others, is now turning to the search for thymus-like tissues in the lamprey. In their 2008 linkurl:study,;http://www.nature.com/ni/journal/v9/n3/abs/ni1562.html Cooper's lab reported that the lamprey's B-cell-like lymphocytes (VLRBs) were likely generated in an invagination near the intestine called the typhlosole. "Now there are lots of tools that can be used to go back and reexamine the question," said Cooper, adding that he and his colleagues plan to use chemokines and cytokines to molecularly probe for thymus-like tissues in the lamprey. "It will be very interesting to find out if there's something analogous" to the thymus in lampreys, said Rast. "Ten years ago, you really couldn't do anything outside of the jawed vertebrates," he added, but with the genomes of several invertebrate species and that of lampreys set for publication soon, the power to study immunology in a wider range of organisms is growing. "It's a really exciting time," Rast said. "Immunology is really going to expand."
**__Related stories:__***linkurl:Fish virus hits Great Lakes;http://www.the-scientist.com/news/display/53252/
[24th May 2007]*linkurl:Lamprey immunity;http://www.the-scientist.com/article/display/43705/
[February 2007]*linkurl:Evolution of innate immunity;http://www.the-scientist.com/article/display/22271/
[8th July 2004] __Editor's note (June 1): This article has been updated from a previous version.__