title: B-cell very late antigen-4 deficiency reduces leukocyte recruitment and susceptibility to central nervous system autoimmunity.
abstract: Natalizumab, which binds very late antigen-4 (VLA-4), is a potent therapy for multiple sclerosis (MS). Studies have focused primarily upon its capacity to interfere with T-cell migration into the central nervous system (CNS). B cells are important in MS pathogenesis and express high levels of VLA-4. Here, we report that the selective inhibition of VLA-4 expression on B cells impedes CNS accumulation of B cells, and recruitment of Th17 cells and macrophages, and reduces susceptibility to experimental autoimmune encephalomyelitis. These results underscore the importance of B-cell VLA-4 expression in the pathogenesis of CNS autoimmunity and provide insight regarding mechanisms that may contribute to the benefit of natalizumab in MS, as well as candidate therapeutics that selectively target B cells.
authors.affiliation: Department of Neurology, University of California; Program in Immunology, University of California, San Francisco, San Francisco, CA.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lehmann-Horn
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Sagan
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Sobel
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D039041:Integrin alpha4beta1 / Q000172:deficiency*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1