How do CD20-depleting antibodies work..To T or Not to T that is the Question.

As soon as rituximab and then ocrelizumab, which are both CD20 depleting antibodies, were shown to influence relapsing MS, implicating B cells as a target for MS.

We had a flow of papers indicating that T cells express weak amounts of CD20. This view is trotted out time and time again, if you mention B cells as an issue.

These T cells are depleted by rituximab and so the T cell biologists have clung to the idea that rituximab works by depleting T cells.

Palanichamy A, Jahn S, Nickles D, Derstine M, Abounasr A, Hauser SL, Baranzini SE, Leppert D, von Büdingen HC. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J Immunol. 2014;193:580-586.

Is this a desperate view to cling to? 

I think so

(A) The Tcellers are happy to accept that depleting 5% of T cells (i.e. the CD20+ T cell subsets) inhibits MS, whilst dismissing the fact that 70% depletion of (CD4) has minimal effect. This makes minimal sense to me

(B) However, it is not only CD20 that implicates activity on B cells. 

Do T cells express Bruton Tyrosine Kinase and CD19, because these B cell depleting agents also work in relapsing MS.

The answer is here.

Schuh E, Berer K, Mulazzani M, Feil K, Meinl I, Lahm H, Krane M, Lange R, Pfannes K, Subklewe M, Gürkov R, Bradl M, Hohlfeld R, Kümpfel T, Meinl E, Krumbholz M. Features of Human CD3+CD20+ T Cells. J Immunol. 2016;197:1111-7. 


"These cells display a lower level of CD20 than B cells and lack markers typically found on B cells such as HLA-DR, CD40 and CD19".

"We sorted CD3+CD20+ cells, CD3+CD20 T cells, and CD19+CD20+ B cells from healthy donors to compare their transcript levels of CD3, CD19, and CD20 by quantitative PCR"......they got


Yep the same result, the CD20+ T cells are not going to be hit by CD19-depleting antibodies.

So can the effect of CD19 depleting antibodies be explained via a T cell mechanism?

Maybe its time to think that really CD20 works, because its depleting B cells.

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