UPDATE: Slides added
So much fun was had, that ProfG has gone for Round Two, and this time has persuaded ProfB (Lightweight) to take the challenge to Heinz Weindl (Heavy Weight). Today
But to make it easier for Prof Weindl to accept the challenge, the loop-hole has been closed so that the T and B cells can be the problem as you have to explain how ocrelizumab works, which was the majority view expressed at ECTRIMS, when given the Choice.
The motion is
“To B or not-T-B that is the question”; the key pathogenic cell in MS is a B-cell and is independent of antigen presentation to T-cells”
Sounds like ProfB is in for a verbal kicking from the opponent and probably the audience.
However, when the vote went live to twitter sphere after people had watched the videos and could not say both
We have a victim the Ms. Oligodendrocyte has been murd**ed (killed). (If I use the word m******d, it triggers google to make this an adult site).
Where did the event take place?
What was the killing weapon?
The punishment will be the Death Penalty for the Guilty Party unless there can be rehabilitation.
The debate isn’t being filmed, but we will rehearse the arguments from both side after the debate.
Here are the slides (The Jokes have been removed)
As you can see the task given to ProfB was to argue that B cells can cause MS and this was not mediated by T cells and the activity due to B cells was not antigen presentation.
This view was against what most people thought (about 60%).
(a) The Key Idea presented was that the important subsets would come from looking at the response to therapy.
(b) It was argued by the audience that animal studies show that B cells present antigens to T cells in animals.
It was said because MOG T cell receptor transgenic (developed optic neuritis but not EAE) x MOG B cell receptor (immunoglobulin) transgenic mice (do not get EAE) get EAE means that B cells present antibody to T cells.
This is not necessarily right as MOG T cell receptor transgenic mice, which get optic neuritis in both eyes, get sub-clinical spinal cord EAE. Add anti-MOG antibody and you get augmentation of disease and this can make mice develop clinical EAE, so no B cell presentation occurring.
Although B cells may well present antigens and there is evidence to support, this based on my extreme stance is irrelevant as animal models lack validity, because the CD20 depleting antibodies have a modest/marginal effect compared to that seen in humans. We know animal models are T cell mediated. The aim here was not to discuss any of the animal work. MS is a human disease let’s have a human based explanation
(c) Importantly the case was made that T cell depletion had a marginal effect. Now I could argue why the T cell depletion trials had not worked but I was attacking this view,
Again there was uproar by the T cell immunologists when it was suggested by that their much loved Th17 cells didn’t do much in MS.
This was contentious as expected. The audience and Prof W argued that IL-17A blockage didn’t fail…ProfB’s response was he didn’t say it failed, he said it was no better than beta interferon, which is hardly a view that interleukin 17 was something magic.
The primary endpoint did not reach significance and so the study failed….That’s how we do trials.
De Stefano N, Curtin F, Stubinski B, Blevins G, Drulovic J, Issard D, Shotekov P, Gasperini C; IMPROVE Study Investigators.
Rapid benefits of a new formulation of subcutaneous interferon beta-1a in relapsing-remitting multiple sclerosis. Mult Scler. 2010; 16(7):888-92.
So anti-IL17 is hardly in the league of something like natalizumab.
Were the T cell immunologists deluding themselves?
(d) The argument was made that Tcellers stop people understanding of how MS works because they view MS as a single cell type. This was clearly evident in the argument of ProfW
(d) An argument was that memory B cells and EBV was interlinked
The question was asked if you have antigen specific B cells, there must be antigen specific T cells. What are they doing?
If the question was turned around and you ask a T celler, what are the antigen specific B cells doing? The answer may be who cares about B cells.
However, if EBV is driving the memory B cell activity,
Does there need to be a T cell help as the virus can make naive B cells proliferate and differentiate into memory B cells and this could be without T cells
There are testable hypothesis that come for these studies,
I suspect the T cellers will continue with their T cell stuff as usual. This is fine meaning we can do it.
However, there was enough open-minded people in the audience to see sense and they are the people who may be treating you.