The macrophage migration inhibitory factor pathway in human B cells is tightly controlled and dysregulated in multiple sclerosis. Issue 11 (25th September 2018)

• Record Type: Journal Article
• Authors: Rijvers, Liza; Melief, Marie‐José; van der Vuurst de Vries, Roos M.; Stéphant, Maeva; van Langelaar, Jamie; Wierenga‐Wolf, Annet F.; Hogervorst, Jeanet M.; Geurts‐Moespot, Anneke J.; Sweep, Fred C. G. J.; Hintzen, Rogier Q.; van Luijn, Marvin M.
• Is Part Of: European journal of immunology. Volume 48:Issue 11(2018)
• Page Start: 1861
• Page End: 1871
• Publication Date: 2018-09-25
• Subjects: Autoimmune disease -- B‐cell biology -- Clinically isolated syndrome -- MIF receptors CXCR4/CD74 -- MS; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847623
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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. Abstract : Our study reveals that CD74 is downregulated and CXCR4 is upregulated on peripheral B cells during MS onset. The expression of these MIF receptors is mutually regulated and selectively controls the proliferative, proinflammatory, and survival capacity of B cells. This provides new insights into their role as drivers of MS.