1. Neutrophils promote VLA-4-dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation.
- Author
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Parker Harp CR, Archambault AS, Cheung M, Williams JW, Czepielewski RS, Duncker PC, Kilgore AJ, Miller AT, Segal BM, Kim AHJ, Randolph GJ, and Wu GF
- Subjects
- Animals, Antigen Presentation, B-Lymphocytes pathology, Chemokines metabolism, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental pathology, Female, Integrin alpha4beta1 immunology, Lymphoid Tissue immunology, Lymphoid Tissue pathology, Male, Meninges pathology, Meningitis immunology, Meningitis pathology, Mice, Inbred C57BL, Multiple Sclerosis immunology, Myeloid Cells pathology, Neutrophils immunology, Neutrophils pathology, Rabbits, Receptors, Interleukin-8B metabolism, Subarachnoid Space pathology, B-Lymphocytes immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Integrin alpha4beta1 metabolism, Meninges immunology, Multiple Sclerosis pathology
- Abstract
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., Competing Interests: The authors declare no competing interest., (Copyright © 2019 the Author(s). Published by PNAS.)
- Published
- 2019
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