文章基本信息

标题：Neutrophils promote VLA-4–dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation
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作者：Chelsea R. Parker Harp ; Angela S. Archambault ; Matthew Cheung 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2019
卷号：116
期号：48
页码：24221-24230
DOI：10.1073/pnas.1909098116
出版社：The National Academy of Sciences of the United States of America
摘要：The success of B cell depletion therapies and identification of leptomeningeal ectopic lymphoid tissue (ELT) in patients with multiple sclerosis (MS) has renewed interest in the antibody-independent pathogenic functions of B cells during neuroinflammation. The timing and location of B cell antigen presentation during MS and its animal model experimental autoimmune encephalomyelitis (EAE) remain undefined. Using a new EAE system that incorporates temporal regulation of MHCII expression by myelin-specific B cells, we observed the rapid formation of large B cell clusters in the spinal cord subarachnoid space. Neutrophils preceded the accumulation of meningeal B cell clusters, and inhibition of CXCR2-mediated granulocyte trafficking to the central nervous system reduced pathogenic B cell clusters and disease severity. Further, B cell-restricted very late antigen-4 (VLA-4) deficiency abrogated EAE dependent on B cell antigen presentation. Together, our findings demonstrate that neutrophils coordinate VLA-4–dependent B cell accumulation within the meninges during neuroinflammation, a key early step in the formation of ELT observed in MS.
关键词：B cell ; EAE ; multiple sclerosis