Friday, 15 January 2016

B cells present antigen

Nielsen CH, Börnsen L, Sellebjerg F, Brimnes MK.Myelin Basic Protein-Induced Production of Tumor Necrosis Factor-α and Interleukin-6, and Presentation of the Immunodominant Peptide MBP85-99 by B Cells from Patients with Relapsing-Remitting Multiple Sclerosis. PLoS One. 2016;11(1):e0146971.

B cells are involved in driving relapsing-remitting multiple sclerosis (RRMS), as demonstrated by the positive effect of therapeutic B-cell depletion. Aside from producing antibodies, B cells are efficient antigen-presenting and cytokine-secreting cells. Diverse polyclonal stimuli have been used to study cytokine production by B cells, but here we used the physiologically relevant self-antigen myelin basic protein (MBP) to stimulate B cells from untreated patients with RRMS and healthy donors. Moreover, we took advantage of the unique ability of the monoclonal antibody MK16 to recognize the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide. The proportions of B cells producing TNF-α or IL-6 after stimulation with MBP were higher in RRMS patients than in healthy donors, indicating a pro-inflammatory profile for self-reactive patient B cells. In contrast, polyclonal stimulation with PMA + ionomycin and MBP revealed no difference in cytokine profile between B cells from RRMS patients and healthy donors. Expanded disability status scale (EDSS) as well as multiple sclerosis severity score (MSSS) correlated with reduced ability of B cells to produce IL-10 after stimulation with MBP, indicative of diminished B-cell immune regulatory function in patients with the most severe disease. Moreover, EDSS correlated positively with the frequencies of TNF-α, IL-6 and IL-10 producing B cells after polyclonal stimulation. Patient-derived, IL-10-producing B cells presented MBP85-99 poorly, as did IL-6-producing B cells, particulary in the healthy donor group. B cells from MS patients thus present antigen to T cells in a pro-inflammatory context. These findings contribute to understanding the therapeutic effects of B-cell depletion in human autoimmune diseases, including MS
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http://www.intechopen.com/source/html/39812/media/image1.jpeg
It is clear that anti-CD20 antibodies can inhibit relapsing disease. But how is it doing it. ProfG has suggested that it is killing B cells that harbour EBV, however immunologists argue that it is blocking presentation of antigen. Indeed this is supported in this study.

3 comments:

  1. "The proportions of B cells producing TNF-α or IL-6 ..."
    "EDSS correlated positively with the frequencies of TNF-α, IL-6..."

    IL-6 plays also a big role in the permabilty of the BBB.
    IL-6 knockout mice don't get EAE
    Il-6 mice with increased IL-6 levels produce a variety of neurologocal symptoms
    Smoking increases IL-6 levels
    VitD3 reduces IL-6 levels
    ALL effective drug in MS reduce IL-6
    IL-6 is measured at increased levels when a lesion is present
    EGCG inhibts IL-6 levels
    IL-17 increases IL-6 levels
    IL-6 produces MORE IL-6
    IL-6 levels are increased at times with stress
    IL-6 inhibts INF-b1 (the reason why some pwMS don't respond to INF-b?

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  2. The assumption here is that myelin basic protein is a relevant antigen. But is it? The real reason to look at MBP in this paper is methodological: "we took advantage of the unique ability of the monoclonal antibody MK16 to recognize the immunodominant peptide MBP85-99 presented on HLA-DR15, and used it as a probe to directly study B-cell presentation of self-antigenic peptide". IT would be more interesting to actually identify the self-antigen (if it exists)

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    Replies
    1. Yeah, that's what I wonder also if the B cells present antigens the T cells, and if supposedly anti-CD20 prevent this antigen reached T cells, then what or who would be such an antigen or autoantigen?

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