Tuesday, 31 December 2013

B cells act as antigen presenting cells

Molnarfi N, Schulze-Topphoff U, Weber MS, Patarroyo JC, Prod'homme T, Varrin-Doyer M, Shetty A, Linington C, Slavin AJ, Hidalgo J, Jenne DE, Wekerle H, Sobel RA, Bernard CC, Shlomchik MJ, Zamvil SS. MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J Exp Med. 2013 Dec. [Epub ahead of print]


Whether B cells serve as antigen-presenting cells (APCs) for activation of pathogenic T cells in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) is unclear. To evaluate their role as APCs, we engineered mice selectively deficient in MHC II on B cells (B-MHC II-/-), and to distinguish this function from antibody production, we created transgenic (Tg) mice that express the myelin oligodendrocyte glycoprotein (MOG)-specific B cell receptor (BCR; IgHMOG-mem) but cannot secrete antibodies. B-MHC II-/- mice were resistant to EAE induced by recombinant human MOG (rhMOG), a T cell- and B cell-dependent autoantigen, and exhibited diminished Th1 and Th17 responses, suggesting a role for B cell APC function. In comparison, selective B cell IL-6 deficiency reduced EAE susceptibility and Th17 responses alone. Administration of MOG-specific antibodies only partially restored EAE susceptibility in B-MHC II-/- mice. In the absence of antibodies, IgHMOG-mem mice, but not mice expressing a BCR of irrelevant specificity, were fully susceptible to acute rhMOG-induced EAE, also demonstrating the importance of BCR specificity. Spontaneous opticospinal EAE and meningeal follicle-like structures were observed in IgHMOG-mem mice crossed with MOG-specific TCR Tg mice. Thus, B cells provide a critical cellular function in pathogenesis of central nervous system autoimmunity independent of their humoral involvement, findings which may be relevant to B cell-targeted therapies.
The EAE brigade has built the picture that MS is a T cell mediated disease but this has not been compellingly shown and then we have the bombshell that anti-CD20 B cell therapy appears to block relapsing MS. So how does this happen,it is because T cells express CD20 and this subset of cells cause MS,is it because B cells act as antigen presenting cells or is it because B cells contain the aetiological factor such as EBV and so getting rid of them blocks the trigger. This study argues that B cells are involved in antigen presentation as the authors and others have suggested in the past

Antigen presentation to CD4 cells requires MHC class II and in this study they stopped B cells producing MHC class II and they did not get EAE, suggesting that B cells are active as antigen presenting cells and EAE could develop in the abense of an anti-myelin antibody response, but I guess we knew this already from many previous studies, including the finding that EAE can develop in B cell deficient mice

This gives an idea how rituximab and ocrelizumab works

2 comments:

  1. Mouse,

    Thanks for this post.

    How good are Rituximab and Ocrelizimab. I know that iterferons cut relapses by 30 per cent, gilenya by 50, tysabri by 65. I don't recall seeing similar numbers for the B cell depleters. Also, if they work because they kill cells with EBV, what will the Charcot project be doing ie doing differently?

    Make sure you take some days off!

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    Replies
    1. They are in the range of the tysabri/glenya.

      If they work by killing B cells and EBV that is what the Charcot aims to do.however the difference is the risk profile there have been PML with rituximab but raltegrevir is much safer.

      Ta I've had a few

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