Lehmann-Horn K, Sagan SA, Winger RC, Spencer CM, Bernard CC, Sobel RA, Zamvil SS.CNS accumulation of regulatory B cells is VLA-4-dependent.Neurol Neuroimmunol Neuroinflamm. 2016 ;3(2):e212.
OBJECTIVE:To investigate the role of very late antigen-4 (VLA-4) on regulatory B cells (Breg) in CNS autoimmune disease.
METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced in mice selectively deficient for VLA-4 on B cells (CD19cre/α4(f/f)) by immunization with myelin oligodendrocyte glycoprotein (MOG) peptide (p)35-55 or recombinant human (rh) MOG protein. B-cell and T-cell populations were examined by flow cytometry and immunohistochemistry. Breg were evaluated by intracellular IL-10 staining of B cells and, secondly, by coexpression of CD1d and CD5.
RESULTS: As previously reported, EAE was less severe in B-cell VLA-4-deficient vs control CD19cre mice when induced by rhMOG, a model that is B-cell-dependent and leads to efficient B-cell activation and antibody production. Paradoxically, B-cell VLA-4-deficient mice developed more severe clinical disease than control mice when EAE was induced with MOG p35-55, a B-cell-independent encephalitogen that does not efficiently activate B cells. Peripheral T-cell and humoral immune responses were not altered in B-cell VLA-4-deficient mice. In MOG p35-55-induced EAE, B-cell VLA-4 deficiency reduced CNS accumulation of B but not T cells. Breg were detected in the CNS of control mice with MOG p35-55-induced EAE. However, more severe EAE in B-cell VLA-4-deficient mice was associated with virtual absence of CNS Breg.
CONCLUSIONS: Our results demonstrate that CNS accumulation of Breg is VLA-4-dependent and suggest that Breg may contribute to regulation of CNS autoimmunity in situ. These observations underscore the need to choose the appropriate encephalitogen when studying how B cells contribute to pathogenesis or regulation of CNS autoimmunity.
Is EAE being turned in to a B cell disease as ocrelizumab gets nearer the clinic.
This study says that rather than have consistent disease severity in your experiments if you want to get your treatment to have a lesser effect, make sure you have a control score of mean 4, but if you want to show that your treatment makes things worse make sure your control group is mean 2:-)
Only kidding. It says that you have to induce your disease in a certain way do it with whole protein you get one thing do it with a peptide of the same protein you get a different thing. It has been argued that it is all to so with processing of antigen, but in this study it says if you block the target for natalizumab then B regulatory cells don't get into the CNS and have more severe disease, so does this tell us that the role of natalizumab is to block T cells because if the major action was on the B cell then would MS not get worse?. So more support for the role of T cells in MS. However, if you look at the disease profile it suggests that the influence is not on disease development but on disease inhibition once started.
Labels: B Cells, fingolimod; natalizumab