Thursday, 29 October 2015

B cells assume control


Li R, Rezk A, Miyazaki Y, Hilgenberg E, Touil H, Shen P, Moore CS, Michel L, Althekair F, Rajasekharan S, Gommerman JL, Prat A, Fillatreau S, Bar-Or A; Canadian B cells in MS Team. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.Sci Transl Med. 2015 Oct 21;7(310):310ra166. doi: 10.1126/scitranslmed.aab4176.

B cells are not limited to producing protective antibodies; they also perform additional functions relevant to both health and disease. However, the relative contribution of functionally distinct B cell subsets in human disease, the signals that regulate the balance between such subsets, and which of these subsets underlie the benefits of B cell depletion therapy (BCDT) are only partially elucidated. We describe a proinflammatory, granulocyte macrophage-colony stimulating factor (GM-CSF)-expressing human memory B cell subset that is increased in frequency and more readily induced in multiple sclerosis (MS) patients compared to healthy controls. In vitro, GM-CSF-expressing B cells efficiently activated myeloid cells in a GM-CSF-dependent manner, and in vivo, BCDT resulted in a GM-CSF-dependent decrease in proinflammatory myeloid responses of MS patients. A signal transducer and activator of transcription 5 (STAT5)- and STAT6-dependent mechanism was required for B cell GM-CSF production and reciprocally regulated the generation of regulatory IL-10-expressing B cells. STAT5/6 signaling was enhanced in B cells of untreated MS patients compared with healthy controls, and B cells reemerging in patients after BCDT normalized their STAT5/6 signaling as well as their GM-CSF/IL-10 cytokine secretion ratios. The diminished proinflammatory myeloid cell responses observed after BCDT persisted even as new B cells reconstituted. These data implicate a proinflammatory B cell/myeloid cell axis in disease and underscore the rationale for selective targeting of distinct B cell populations in MS and other human autoimmune diseases.

A proinflammatory B cell cytokine activates autoimmunity, and B cell depletion treats multiple sclerosis. In this study a cytokine turned on pathogenic cells and countered the IL-10 producing regulatory B cells, so bring on ant-CD19 andti CD20.

We will slow see EAE turned into a B cell disease

7 comments:

  1. Prof M,

    This study got lots of coverage a couple of days ago. Is it a big finding? Please leave those poor mice alone. If we have B cell depleting human trials underway, we don't need an animal model. eaeologists are like economists - they see something working in practice and wonder if it will work in theory (Ronald Reagan). Where's Prof G? I think he has fallen out with the other members of Team G. Perhaps he objected to the Halloween Party which he wasn't invited to. Perhaps he's upset with SA in the rugby. Give him a hug Prof M - sometimes a big shot prof needs some love.

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  2. I'm sort of new to this blog.
    Could someone explain me why there are periodically some angry comments like the one above, posted by some brave people who "omit" to tag their name on ?
    I mean, this blog is a very important source of information for the MSers group which I belong to. Please respect that. I don't know ... write him an email ^^

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    1. I think its meant humourously, if that's any help. Perhaps the poster will get back to you and explain their comments (he/she is a regular contributor), maybe even adding a name.
      We get all sorts of flavour of comments on the blog, the really nasty ones we bin to protect the sensibilities of our readers ;-)

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  3. I know that anti-CD20 mAbs are on the market and in late stage trials. It looks like anti-CD19 mAbs are still in the lab; is this correct? What additional does an anti-CD19 mab offer over anti-cd20?

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  4. What does this study have to do with EAE? They just did some cell culture on human B cells.

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    1. You're right this study has nothing to do with EAE but as MD says it'll be interesting to see if EAEers (primarily T cell T cell T cell) will attempt to jump on the B cell bandwagon.

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  5. I feel like that post was genuinely in jest? Hence the rugby reference.

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