@article{9e605d4eee0442b296387c766e7b5064,
title = "Neutrophils promote VLA-4–dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation",
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.",
keywords = "B cell, EAE, Multiple sclerosis",
author = "{Parker Harp}, {Chelsea R.} and Archambault, {Angela S.} and Matthew Cheung and Williams, {Jesse W.} and Czepielewski, {Rafael S.} and Duncker, {Patrick C.} and Kilgore, {Aaron J.} and Miller, {Aidan T.} and Segal, {Benjamin M.} and Kim, {Alfred H.J.} and Randolph, {Gwendalyn J.} and Wu, {Gregory F.}",
note = "Funding Information: We thank Denise Dorsey, Christine Pham, Mary Dinauer, and Julia Sim for research advice and Thalia Papayannopoulou at the University of Washington for kindly providing itga4f/f mice. We would also like to thank Diane Bender and Michael Shih at Washington University for technical assistance. The National Institute of Neurological Disorders and Stroke supported C.R.P.H. (F31NS096824) and G.F.W. (R01NS106289). Research reported herein was supported by the Immunomonitoring Laboratory within The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs at Washington University in St. Louis. Funding Information: ACKNOWLEDGMENTS. We thank Denise Dorsey, Christine Pham, Mary Dinauer, and Julia Sim for research advice and Thalia Papayannopoulou at the University of Washington for kindly providing itga4f/f mice. We would also like to thank Diane Bender and Michael Shih at Washington University for technical assistance. The National Institute of Neurological Disorders and Stroke supported C.R.P.H. (F31NS096824) and G.F.W. (R01NS106289). Research reported herein was supported by the Immunomonitoring Laboratory within The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs at Washington University in St. Louis. Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = nov,
day = "26",
doi = "10.1073/pnas.1909098116",
language = "English",
volume = "116",
pages = "24221--24230",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "48",
}