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    Evolution of Antigen Presenting Cells in the Spleen

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    Author
    Flowers, Emily Maya
    0000-0003-4803-3824
    Advisor
    Flajnik, M. F. (Martin F.)
    Date
    2021
    Type
    dissertation
    
    Metadata
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    Abstract
    XL cells are an MHC class IIhigh, cell surface-absorbed-Ig+ population of antigen presenting cells in the B cell follicle of the amphibian spleen. XL cells bear native antigen after immunization. Previous work proposed that XL cells are “double-duty” antigen presenting cell (APC), presenting antigen to both T and B cells. In mammals these functions are generally partitioned between conventional dendritic cells (cDC) presenting to T cells and follicular dendritic cells (FDC) presenting to B cells. In this PhD I have expanded on that premise, by comparing XL cells and peritoneal macrophages via RNA sequencing, functional assays, and in vivo kinetics of antigen handling. Like XL cells, Xenopus peritoneal macrophages are an MHC-IIhigh / Ig+ population. However, peritoneal macrophages are highly adherent, esterase-positive, and phagocytic, while my data demonstrate that XL cells are weakly adherent, esterase-low/negative, and weakly phagocytic. The peritoneal macrophage transcriptome is consistent with the broad myeloid lineage, and MAFB and CEBPA expression specifically within the macrophage lineage. XL cells express higher levels of genes associated with myeloid cDCs and cDC precursors, specifically ID2, BATF3, IRF4, and CD209. When formally testing the similarity between Xenopus and mammalian cell types, XL cells were enriched for cDC genes. In vivo, XL cells retain antigen through approximately day 20 after immunization – far shorter than the FDC antigen retention. Overall XL cells transcriptionally resemble mammalian cDC but share functional genes with FDC. We posit that XL cells are the myeloid precursor to FDC function, but also represent an evolutionary precursor to dedicated cDC lineages.
    Description
    University of Maryland, Baltimore. Molecular Microbiology and Immunology. Ph.D. 2021
    Keyword
    comparative immunology
    Dendritic Cells
    Biological Evolution
    Dendritic Cells, Follicular
    Macrophages
    Xenopus
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/17939
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