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The next step in understanding tolerance (Part 3)

RELATED STORIES

The next step in understanding tolerance (Part 2)
Avrion Mitchison Scientist
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So the role of the thymus, the ability to do serology, and I think I should add to serology the ability to detect platforming cells, that was a technique used by Miller for his work on TB co-operation and it's important to know. And then adopted transfer, the ability to transfer lymphocytes and get them to perform in another mouse, but we've already talked about that. So, I think that's sort of the three groups. Would you agree? Yes. Yes. Yes. So, then there were, world-wide, four groups became interested in the relationship between these T-cells and the cells which make antibody, which were known to be derived from bone marrow. One group, and probably the first group to become interested in that, was the Benacerraf group, with a lot of input from Phillip Jell from Birmingham, who used to go over and work with Benasarref. A second group was Jacques Miller and his colleagues in Melbourne in the Walter and Eliza Hall Institute there. The third group was us, that's you and me, Martin, in NIMR, National Institute of Medical Research, and the fourth was Klaus Rajewsky and his colleagues in Cologne. So I think we have to, sort of, look at the work in those four streams. Benacerraf and Jale had shown that, in the cellular response, and their example of cellular response wasn't transplantation, it was skin hypersensitivity, different parts of a protein are recognised by antibody. So, there were two kinds of antigens, those which turned on T-cell responses, and those which turned on B-cell responses, and Benacerraf became attached to the idea that what was special about the T-cell was that it might have a receptor which saw not the little bit of a protein which an antibody saw, but the whole of the molecule, or a large part of the molecule. So it saw- When you looked at a guinea pig showing delayed hypersensitivity to the dinitrophenol group because that was an experiment he was fond of, he and Jale were very fond of, the T-cells were recognising not the dinitrophenol group, but the dinitrophenol group plus the local environment on the protein when it was found. So that type of hypothesis got to be called the local environment hypothesis. Jacques Miller was studying the contribution of the thymus, and he showed that thymectomised mice didn't make an antibody response using this platforming cell, PSC assay, that I mentioned, the spleen didn't have cells which could be enumerated by their ability to make a antibody against sheep red cells. Cut out the spleen, that didn't happen. But he then showed, by transfer experiments, that- Sorry, just to back up, you cut out the thymus and that didn't happen? It didn't happen. Right. That what was missing was not the cells which were making antibodies themselves, but cells derived from a thymus which helped those cells to make antibodies. And he did that by a number of ingenious experiments. Perhaps the best was to take cells from the thymus, put them into one mouse, immunise them there, and then transplant them into a third mouse, also irradiated, where they had B-cells to help them, and he could show that the antibody was then being made by the B-cells, but the cells which- priming the thymus cells, that made them better able to co-operate with B-cells.

Avrion Mitchison, the British zoologist, is currently Professor Emeritus at University College London and is best known for his work demonstrating the role of lymphocytes in tumour rejection and for the separate and cooperative roles of T- and B-lymphocytes in this and other processes.

Listeners: Martin Raff

Martin Raff is a Canadian-born neurologist and research biologist who has made important contributions to immunology and cell development. He has a special interest in apoptosis, the phenomenon of cell death.

 

 


Listen to Martin Raff at Web of Stories

 

 

Duration: 4 minutes, 29 seconds

Date story recorded: June 2004

Date story went live: 24 January 2008