About a decade ago, Stanford Bio-X director Carla Shatz, PhD, found that some proteins from the immune system seemed to be playing a role in the brain. Not all scientists were on board with the protein’s double life. Then Ben Barres, MD, PhD, a neurobiologist at Stanford, started finding the same thing with a different set of proteins – these immune system denizens appeared to be functioning in the brain (here’s a write-up on that work by my colleague Bruce Goldman). And still, not all immunologists accepted that the brain might also be using these proteins.
Now Shatz has published a paper online March 30 in Nature that should put the disagreement to rest. She very carefully showed that a protein originally known for its role in the immune system, called MHC Class I D, or D for short, was present in the nerves of the developing brain. She told me, “The nervous system has just as much right to these immune proteins as the immune system.”
The role D plays is in helping the brain trim back connections as it develops. I didn’t know this before working on my story, but the brain starts out with about double the number of nerve connections than it will eventually use. The ones the brain doesn’t use get trimmed back. Shatz studies this process in a part of the brain that tries to create a single view of the world out of signals coming from the two eyes. In my press release I wrote:
Shatz said the rule of which connections the brain cuts back to create that single vision follows a simple mantra: “Fire together, wire together. Out of sync, lose your link.” Or rather, if early in life the left sides of both eyes see the same duck motif wallpaper, those neurons fire together and stay linked up. When the top of one eye and bottom of the other eye form a connection, the nerves fire out of sync, and the connection weakens and is eventually pruned back. Over time, the only connections that remain are between parts of the two eyes that are seeing the same thing.
I spoke with Lawrence Steinman, MD, PhD, a neurologist at Stanford who studies multiple sclerosis, a disease of both the immune system and the nervous system. He has a foot in both worlds and has followed Shatz’ work from the beginning. He says part of the problem in gaining acceptance for Shatz’ findings was in a name. A rose by any name may smell as sweet, but a protein with a name like “major histocompatibility complex I” only sounds to a biologist like an immune protein. He says he teaches students that if Shatz had published her work first the protein would have an entirely different name and it would be the immunologists fighting to claim the protein’s role in their world.
“They clearly have major roles in both the nervous system and the immune system,” he said.