Journal article
Proteolipid Protein–Induced Mouse Model of Multiple Sclerosis Requires B Cell–Mediated Antigen Presentation
The Journal of immunology (1950), Vol.211(6), pp.944-953
09/15/2023
DOI: 10.4049/jimmunol.2200721
PMCID: PMC10528642
PMID: 37548478
Abstract
Abstract The pathogenic role B cells play in multiple sclerosis is underscored by the success of B cell depletion therapies. Yet, it remains unclear how B cells contribute to disease, although it is increasingly accepted that mechanisms beyond Ab production are involved. Better understanding of pathogenic interactions between B cells and autoreactive CD4 T cells will be critical for novel therapeutics. To focus the investigation on B cell:CD4 T cell interactions in vivo and in vitro, we previously developed a B cell–dependent, Ab-independent experimental autoimmune encephalomyelitis (EAE) mouse model driven by a peptide encompassing the extracellular domains of myelin proteolipid protein (PLPECD). In this study, we demonstrate that B cell depletion significantly inhibited PLPECD-induced EAE disease, blunted PLPECD-elicited delayed-type hypersensitivity reactions in vivo, and reduced CD4 T cell activation, proliferation, and proinflammatory cytokine production. Further, PLPECD-reactive CD4 T cells sourced from B cell–depleted donor mice failed to transfer EAE to naive recipients. Importantly, we identified B cell–mediated Ag presentation as the critical mechanism explaining B cell dependence in PLPECD-induced EAE, where bone marrow chimeric mice harboring a B cell–restricted MHC class II deficiency failed to develop EAE. B cells were ultimately observed to restimulate significantly higher Ag-specific proliferation from PLP178–191–reactive CD4 T cells compared with dendritic cells when provided PLPECD peptide in head-to-head cultures. We therefore conclude that PLPECD-induced EAE features a required pathogenic B cell–mediated Ag presentation function, providing for investigable B cell:CD4 T cell interactions in the context of autoimmune demyelinating disease.
Details
- Title: Subtitle
- Proteolipid Protein–Induced Mouse Model of Multiple Sclerosis Requires B Cell–Mediated Antigen Presentation
- Creators
- Connor R. WilhelmMohit A. UpadhyeKathryn L. EschbacherNitin J. KarandikarAlexander W. Boyden
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.211(6), pp.944-953
- DOI
- 10.4049/jimmunol.2200721
- PMID
- 37548478
- PMCID
- PMC10528642
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- DOI: 10.13039/100000002, name: HHS | National Institutes of Health, award: R21AI156123; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: I01BX003677; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: I01CX002319
- Language
- English
- Electronic publication date
- 08/07/2023
- Date published
- 09/15/2023
- Academic Unit
- Pathology
- Record Identifier
- 9984453331502771
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