Neutrophils promote VLA-4–dependent B cell antigen presentation and accumulation within the meninges during neuroinflammation

Chelsea R. Parker Harp, Angela S. Archambault, Matthew Cheung, Jesse W. Williams, Rafael S. Czepielewski, Patrick C. Duncker, Aaron J. Kilgore, Aidan T. Miller, Benjamin M. Segal, Alfred H.J. Kim, Gwendalyn J. Randolph, Gregory F. Wu

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish
Pages (from-to)24221-24230
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number48
StatePublished - Nov 26 2019


  • B cell
  • EAE
  • Multiple sclerosis


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