A recent paper from Max Cooper’s lab at Emory has provided an example of an alternative path for evolution, one that disturbs and complicates our picture of how the immune system might have evolved.
Like discovering a place where everyone drives steam turbine-driven cars. Makes me think about Stephen Jay Gould and how evolution doesn’t always have a defined direction leading up to humans.
A review: the cut-and-error-prone-paste process of V(D)J recombination, which assembles antibody genes, seems to have jumped into the early vertebrate genome hundreds of millions of years ago.
T cells and B cells are two arms of the immune system that resemble each other. One responds to peptides displayed by MHC, a useful tool for fighting viruses inside our cells. The other makes antibodies that bind to antigens and can secrete the antibodies, which are great for clearing nasty pathogens from the blood.
Both have receptors on their surfaces that get rearranged by V(D)J, and the genes look similar. One possible order of events is this: there was a primordial “antigen receptor” bearing cell. V(D)J invades the genome, then this primordial cells splits off into T and B.
But no! Lampreys have cells that look like T and B, without V(D)J or the genes that make it possible, RAG1 and RAG2. One set of cells make secreted “variable lymphocyte receptors” and the other doesn’t. One looks like T and the other looks like B, judging from the genes they express.
Lampreys use another genetic shuffling tool to assemble their VLR genes – looks like gene conversion.
It’s worth pointing out that mice and people get most of their immunological diversity from V(D)J but rabbits and chickens don’t, using gene conversion/hypermutation (a process that may have predated V(D)J).
So it looks like the distinction between T and B may have existed first, before V(D)J complicated matters.
Still puzzling is the apparent absence of MHC and a thymus in lampreys, so what T cells respond to and where they develop in lampreys is unclear.