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Author ORCID Identifier

https://orcid.org/0000-0003-0183-6427

Date Available

1-31-2025

Year of Publication

2024

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Medicine

Department/School/Program

Neuroscience

Faculty

Dr. Ann Stowe

Faculty

Dr. Warren Alilain

Abstract

Age-Associated B cells (ABCs) are atypical memory B cells commonly expressing CD11b, CD11c, and T-bet. We hypothesized that aged female mice would have worse functional outcomes after stroke due to higher brain-localized ABCs. We identified 6 ABC subsets expressed in the brain, with higher levels in uninjured animals versus 3 weeks after stroke. Contradictory to my hypothesis, aged uninjured males with higher numbers of Classical ABCs (CD11bhighCXCR5+/CXCR5-) in the brain exhibited better motor function, though with limited differences by injury or sex for other classical ABC subsets. Rare CD11b+CXCR5+ populations from uninjured mice secreted more IFN-γ when exposed to TLR7/9 agonists or post-stroke plasma. ABCs are prone to IFN-γ and TNF secretion with CXCR5+/- cell counts dependent on injury and treatment. Histology identified for the first time that T-Bet+ ABCs exist in cortical, hippocampal, and cerebellar brain regions of aged mice that was also confirmed in human parenchyma. Overall, these data suggest a supportive albeit pro-inflammatory role for CD19+CD11b+ ABCs in aged uninjured males but does not suggest an increase in cell count long-term post-stroke. While these data add to the limited knowledge of ABC’s role in the brains of post-stroke aged mice, more work is necessary to determine potential therapeutic targets.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2024.399

Funding Information

This study was supported both by the National Institutes of Health T32 “Training in Translational Research in Alzheimer’s and Related Dementias (TRIAD)” AG057461 (2021-2023) and Dr. Stowe's R01 "B Cells Directly Alter Adaptive Plasticity to Support Functional Recovery After Stroke" NS088555 (2019-2024).

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