Defining the Role of B Cells in CNS Demyelination
Abstract
This project is designed to evaluate the effects of CNS B cells on glial cells and myelin integrity in demyelinating disease, usingselective cell depletion approaches including a novel transgenic animal model termed CD19Cre-iCP9. Clinical studies in multiplesclerosis show the effectiveness of B cell depletion therapies, including rituximab and ocrelizumab, although the underlyingmechanisms are not well understood. In preliminary studies, using a combination of EAE and the CD19Cre-iCP9 models, wedepleted B cells specifically in the CNS and found a stabilization of disease and reduction in myelin and axonal damage in thespinal cord. In the current studies, we have systemically depleted B cells in the EAE model and demonstrated rapid functionalrecovery. Analyses of early changes in gene expression in astrocytes and microglia by RNA sequencing following B cell depletionsuggest that inflammatory pathways in astrocytes and changes in microglial-neuron interactions drive disease progression. Bycontrast, improvements in neurovascular functioning are associated with recovery after B cell depletion. These unexpectedfindings have the potential to change our understanding of the role of B cells during disease and myelin repair, and in the comingyear, we will shift our focus to understanding the B cell-neurovascular unit interactions using the CNS selective B cell depletionmodel, evaluating molecular mechanisms and ultrastructural characterization of myelin repair.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2023
- Accession Number
- AD1215930
Entities
People
- Julie Ahn
- Robert Miller
- Yusra Islam
Organizations
- George Washington University