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B ‐cell very late antigen‐4 deficiency reduces leukocyte recruitment and susceptibility to central nervous system autoimmunity
Author(s) -
LehmannHorn Klaus,
Sagan Sharon A.,
Bernard Claude C.A.,
Sobel Raymond A.,
Zamvil Scott S.
Publication year - 2015
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24387
Subject(s) - natalizumab , autoimmunity , multiple sclerosis , experimental autoimmune encephalomyelitis , immunology , pathogenesis , central nervous system , antigen , biology , b cell , t cell , medicine , neuroscience , immune system , antibody
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. Ann Neurol 2015;77:902–908