August 13, 2013
Ancient Immune Cells In Lampreys Similar To Ours, But More Complex
April Flowers for redOrbit.com - Your Universe Online
When biologists study lampreys, they are able to envision the evolutionary past because these jawless specimens represent an early offshoot to the evolutionary tree, before sharks and fish. They have an inconspicuous appearance, but a sophisticated immune system with three types of white blood cells that resemble our B and T cells.
A new study from Emory University School of Medicine and the Max Planck Institute of Immunology and Epigenetics in Freiburg has identified a type of white blood cell in lampreys analogous to the "gamma delta T cells" found in mammals, birds and fish. Among other functions, gamma delta T cells have specialized roles defending the integrity of the skin and intestines.
The study, published in Nature, follows earlier research revealing that cells resembling two main types of white blood cells -- B cells and T cells -- are present in lampreys. B cells can differentiate into antibody-secreting cells in humans. These cells can grab their targets directly, while T cells generally recognize their targets only through cell-to-cell contact.
"We have been able to define another lineage of T-like lymphocytes in lampreys," says Masayuki Hirano, PhD, assistant professor of pathology and laboratory medicine at Emory University School of Medicine and the Emory Vaccine Center. "This suggests that the genetic programs for all three lineages of white blood cells are very ancient."
The results indicate that distinct cells with similar functions to gamma delta T cells might have existed in the last common vertebrate ancestor, before jawed and jawless vertebrates diverged around 500 million years ago.
As the foundation of the adaptive immune system, B and T cells allow mammals, birds and fish to respond to a wide variety of pathogens and "remember" what they’ve encountered. Characteristic proteins are produced by B and T cells. B cells produce antibodies, while T cells produce T cell receptors. Both types of proteins have modular sections that are variable from cell to cell, but they share structural and sequence similarity across species.
Comparable to antibodies and T cell receptors, Lampreys' white blood cells produce proteins with a broad diversity and function. These variable lymphocyte receptor (VLR) proteins, however, do not resemble antibodies structurally. Scientists have found that cells producing VLR-A proteins are roughly comparable to T cells, while VLR-B-producing cells resemble B cells.
The lab of Max Cooper, MD, recently characterized the structure and assembly of a third set of VLR-C genes, in addition to the VLR-A and VLR-B gene families. Cooper is professor of pathology and laboratory medicine at Emory University School of Medicine and the Emory Vaccine Center, and a Georgia Research Alliance Eminent Scholar.
The researchers in the new study have shown that VLR-C proteins are found on a third type of white blood cell that do not produce the other VLR varieties. VLR-C positive cells are the predominant white blood cell type found in lampreys’ skin, and they are more abundant in lamprey larvae.
The same or almost the same protein sequence was displayed by many of the VLR-C proteins found in the lamprey’s skin – resembling the restricted diversity of gamma delta T cells found in the skin of mammals. The VLR-C-positive cells found in lampreys have activated some of the same genes that, in mammals, control the development of gamma delta T cells.