Wednesday, 21 June 2017

B cell dependent EAE

Sefia E, Pryce G, Meier UC, Giovannoni G, Baker D. Depletion of CD20 B cells fails to inhibit relapsing mouse experimental autoimmune encephalomyelitis. Mult Scler Relat Disord. 2017 May;14:46-50. doi: 10.1016/j.msard.2017.03.013.

This paper warns about the value of using mice to understand B cell activity in MS. It looks at a few published studies or mouse studies and asks you to think.

If we look in the abstract in the paper below , the work is now done in a B cell- and antibody-dependent mouse model of MS. 

Is this the beginning of the airbrushing to make EAE into a B cell disease, this current paper says stop it simply isn't a B cell disease, it is a T cell disease, where B cells and B cell products can influence the T cell mediated disease.

So what is this B cell dependent disease. It is MP4-induced EAE in C57BL/6 mice. Kuerten S, Pauly R, Rottlaender A, Rodi M, Gruppe TL, Addicks K, Tary-Lehmann M, Lehmann PV. Myelin-reactive antibodies mediate the pathology of MBP-PLP fusion protein MP4-induced EAE.Clin Immunol. 2011;140:54-62. 

This model only develops when you have antigen presenting B cells. First, how representative is this very artificial system. (left) 

The C57BL/6 is amongst the most EAE resistant mouse strain and it was thought to be resistant to myelin basic protein and spinal cord disease until myelin oligodendrocyte glycoprotein came around. MP4 is a synthetic protein of myelin basic protein and water-soluble peptides of proteolipid protein, which are both not expressed on the surface of myelin and so difficult to target for antibodies. (Although antibodies may bind to epitopes outside and inside the myelin). So it was found that a disease resistant strain, could not develop disease with a weak antigen in that strain, unless it has a full complement of antigen presenting cells. 

Nothing has been done to show the issues are really different from any other T cell dependent EAE. If you add myelin antibodies to T cell EAE, this it makes the disease worse, usually, but that does not make it only B cell dependent. The antibodies also appear to be detected after the clinical disease (figure right).

Do we base our ideas on an outer extreme? 

Do we follow it without question, I suspect I can guess how people will treat this (this from one of the guys that gave us epitope spread). I have heard the view from ProfG, enjoy. 

Is this why natalizumab work's in Crohns too?

Of course not....but had you thinking:-)
(P.S. In the gut cells home using alpha4 beta 7 integrin rather than the brain which use alpha 4 beta 1 integrin. natalizumab block alpha4 integrin

1 comment:

  1. We mice have dedicated years of service and enabled some very effective MS treatments to be produced. Not that I'm biased, but there's very little we can help you with now. Thanks for publishing this latest paper to complement the recent trilogy. My friends and family are very grateful.

    May I respectively request that researchers everywhere follow your lead, hang up their lab coats and put on their reading glasses.

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