The macrophage migration inhibitory factor pathway in human B cells is tightly controlled and dysregulated in multiple sclerosis
In MS, B cells survive peripheral tolerance checkpoints to mediate local inflammation, but the underlying molecular mechanisms are relatively underexplored. In mice, the MIF pathway controls B-cell development and the induction of EAE. Here, we found that MIF and MIF receptor CD74 are downregulated, while MIF receptor CXCR4 is upregulated in B cells from early onset MS patients. B cells were identified as the main immune subset in blood expressing MIF. Blocking of MIF and CD74 signaling in B cells triggered CXCR4 expression, and vice versa, with separate effects on their proinflammatory activity, proliferation, and sensitivity to Fas-mediated apoptosis. This study reveals a new reciprocal negative regulation loop between CD74 and CXCR4 in human B cells. The disturbance of this loop during MS onset provides further insights into how pathogenic B cells survive peripheral tolerance checkpoints to mediate disease activity in MS.
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|European Journal of Immunology|
|Organisation||Department of Immunology|
Rijvers, L, Melief, M.J, van der Vuurst de Vries, R.M, Stéphant, M, van Langelaar, J, Wierenga-Wolf, A.F, … van Luijn, M.M. (2018). The macrophage migration inhibitory factor pathway in human B cells is tightly controlled and dysregulated in multiple sclerosis. European Journal of Immunology. doi:10.1002/eji.201847623