So you make T cell responses after anti-CD20 so is it blocking antigen presentation?

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How does anti-CD20 therapy work?

If you are Mister T cell immunologists they give you number of reasons….Their favourite it is because it is depleting the important T cell subset which express CD20 T cells. You can’t get a paper accepted by the establishment unless you say this is a real possibility, although probably very, very unlikely in my humble opinion.

Why do I think it is unlikely…well there are much simpler experiments that better explain the biology and explain the biology is what it must do…..An effect via B cells is far more the better, likely explanation.

As I said if you use this argument to explain the effects of anti-CD20, then you have to use the same argument to explain anti-CD19 treatment. Anti-CD19 depletes more B cells than anti-CD20 but there is very, very, very, very little CD19 on T cells…Explain this.

Then we have other explanations that I won’t waste my breathe on because the logic for these are holier than a piece of swiss Cheese. The ones that are direct effects via B cells as a better candidate way to explain it is a thought too far for T cell immunologists, so as not to have them choke on their Breakfast I will focus on one.

As I have said it over and over again…You can’t have it both ways. If B cell depletion does something you want, you have to accept that B cells do otherthings and some of them…. you don’t want.

So now we have the antigen-presentation to T cells. This is an idea pushed by the manufacturers

However, COVID-19 comes along and we know that anti-CD20 blocks the formation of antibody production and so you are going to get a blunted vaccine response. This is bad news for the sales department because who is going to want an anti-CD20 when you can’t make a COVID-19 vaccine response compared to other agents were you can.

So the manufacturers are going to be desparate to show that you can make a T cell response to COVID-19, because it means that you may be protected by vaccination and sales can be resumed and I may get asked to report on my ideas that the macrophages and T cells are far more important to control of COVID-19 than antibodies:-).

I went out on a limb to say this in March-April 2020 before we knew anything about COVID-19 and MS and I still think this is valid today. High antibodies may stop the intial infection but if you do get infected the macrophage response is all important and most MS drugs don’t do macrophages

Now a few months ago I said this is fun.“You can’t have it both ways”. If it blocks antigen presentation to T cells to inhibit MS it should block antigen presentation by B cells to make a vaccine response. However, they will be desparate to show that vaccination makes a T cell response indicating antigen presentation occurs, therefore you cannot say CD20-blocks inhibits MS because it simply blocks antigen-presentation. T cell immunologists get more of a squeaky bottom and I have abit of a laugh.

As predicted by me, this has happened and a simple antigen-presentation arguement goes out of the window.

However, some bright spark on the blog used the “Get out of Jail Card” and said that to make a vaccine response you need dendritic cells andor macrophages. So anti-CD20 does not block macrophages/dendritic cells and means if this route is being used it is something that is special to B cells. It makes sense to me I have always thought that you get new immune responses you need dendritic cells in the lymph glands to initiate a T cell response that then helps stimulate the B cell response.. Therefore if memory B cells are presenting something it is a select part of antigen-presentation. Some may argue they are presenting a self-antigen to T cells that cause MS, but what ever it is T cells have already seen it and are activated to it.

So it says that what ever anti-CD20 is doing it is not blocking stimulating new responses…The conventional view is external antigens are recognized and captured by B cells through their B cell receptor (BCR). Therefore B cell present what they have an antibody for. Second, the antigen is processed by degrading the antigen in internal compartments within the B cell and then the corresponding peptide fragments are loaded on MHC class II molecules; and third, MHC class II–peptide complexes are presented to CD4+ T cells.

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MouseDoctor

2 comments

  • So making a bit of a leap into a different subject, could it be that “smouldering” MS activity is carried out by T cells that still “remember” the instructions from the now long-absent B cells?

    • Maybe there is a new bandwagon of tissue resident T cells.. I think the smoulding lesions are glia/macrophagel issues. The B cells are ever present oligoclonal bands and all that

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