Friday, 10 February 2017

Is this the Memory B cell target

Li-R et al. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy.Sci Transl Med. 2015 Oct 21;7(310):310ra166.

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.

We have been talking about B cells as a target for MS for the past week and this little gem slipped through the net when it was published last year. 

Is this the target for therapy...We will need to see what happens to this type of cell following treatment. They increase in MS do they get decreased by all active drugs?. 

3 comments:

  1. I like what I've been seeing about B cells this week because I'm (personally) of the opinion that B cells are really the "problem" rather than T cells.

    As a "last question" for this week I'd like to ask whether B cells are really a target because of their (mis-)behavior or just because they are a harbor for EBV? Could it be that MS isn't autoimmune at all but a normal immune process where the immune system is trying to eradicate the EBV that it keeps seeing everywhere? Thus, by eradicating EBV we eradicate MS?

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    Replies
    1. If you read the last paragraph of our B cell paper, indeed this is indicated as a possibility. We keep an open mind sadly many people wont and its back to usual T cell business as usual.

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