How does anti-CD20 work?….Boy are we making it complicated

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Understanding CD20+ T cells in MS

Anti-CD20 monoclonal antibodies have shown some efficacy in patients with multiple sclerosis (MS). Although CD20 is mostly expressed by B cells, a subpopulation of CD20+ T cells has been identified. The origin of CD20+ T cells and their role in autoimmune diseases are not fully elucidated. Now, Ochs et al. found that T cells can acquire CD20 directly from B cells via tragocytosis. In mice with experimental autoimmune encephalomyelitis (EAE) and in patients with MS, expansion of this population contributes to the ongoing pathological inflammatory process. Selective depletion of CD20+ T cells in EAE mice had therapeutic effects, suggesting that elimination of this population might contribute to the efficacy of anti-CD20 therapies in MS.

The origin and function of CD20+ T cells are poorly understood. Here, we characterized CD20+ T cells in mice and humans and investigated how they are affected by anti-CD20 antibody treatment. We report that murine CD20+ T cells are unable to endogenously express the B cell lineage marker CD20; the development of CD20+ T cells in rodents requires the presence of CD20-expressing B cells. Our results demonstrated that both murine and human T cells acquire CD20 from B cells via trogocytosis while being activated by an antigen-presenting B cell. In patients with multiple sclerosis (MS) and mice with experimental autoimmune encephalomyelitis (EAE), expression of CD20 on T cells is associated with an up-regulation of activation markers, proinflammatory cytokines, and adhesion molecules, suggesting high pathogenic potential. Supporting this hypothesis, CD20+ T cells expand during active EAE in rodents; furthermore, adoptive transfer of CD20+ T cells into EAE-diseased mice worsened histological and clinical severity. Of direct therapeutic relevance, we demonstrate that the exclusive therapeutic elimination of CD20+ T cells effectively ameliorates EAE, independent of B cells. The results support the hypothesis that CD20+ T cells arise upon B cell-T cell interaction and that depletion of CD20+ T cells might contribute to the success of anti-CD20 antibody therapies in MS and other inflammatory disorders.

So this paper says T cells do not make CD20 it gets picked up from B cells when they are activating T cells and this is how anti-CD20 works. It seems very complicated to explain it this way and ignore the simple possibility that there is a direct effect on B cells. Especially when in the past it has been argued that anti-CD20 works in B dependent EAE and not in B cell independent EAE.

Trogocytosis (Greek: trogo; gnaw) is when a cell nibbles another cell. It’s a process whereby lymphocytes (B, T and NK cells) conjugated to antigen-presenting cells extract surface molecules from these cells and express them on their own surface.

However if there are no B cells they can’t be nibbled

Disclaimer: This is the views of the author

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MouseDoctor

4 comments

  • I think it’s remarkable how much yet how little we understand about MS and how the different drugs actually work to impact the progression of ms.

  • Does anti cd 20 theraphy inhibit Eae?

    If i recall you say manny moons ago Eae its a t cell disease of mainly the spinal cord
    Thanks

  • My mind is only able to grasp a glib understanding of the distinction you make. I guess I’m surprised there is still so much uncertainty about the role of T and B cells in ms. What do you make of the findings that glatiramer acetate (which I believe is supposed to up regulate good T cells) also reduces the total frequency of B cells, plasmablasts, and memory B cells ? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223706/. is it just more murkiness ? ??

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