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    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2020 Dissertations (MU)
    • 2020 MU dissertations - Access restricted to MU
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    Investigating the deleterious role of B lymphocytes during brucella infection

    Dadelahi, Alexis Setareh
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    [PDF] DadelahiAlexis.pdf (2.773Mb)
    Date
    2020
    Format
    Thesis
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    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Brucellosis is a disease known for inducing chronic, often life-long, infections. While it is clear the host immune response fails to clear Brucella infection, the processes underlying this outcome remain unknown. B cell deficient mice challenged with Brucella display reduced bacterial burden following infection. However, the mechanism driving this resistance is unknown. Here we show B cells only enhance susceptibility to infection when T cells are present. Therefore, we investigated whether B cells inhibit T cell mediated protection against Brucella. Using both adoptive transfer of CD4+ T cells and B cells, as well as CD4+ T cell depletion models, we demonstrated CD4+ T cell mediated immunity against Brucella is inhibited by the presence of B cells. This effect was MHCII-dependent, suggesting a role for B cell antigen presentation in enhancing susceptibility to infection. Indeed, we determined that both B cell-specific MHCII deficiency and Btk deficiency in mice resulted in enhanced resistance to infection. Additionally, B cell receptor specificity contributed to both resistance as well as Brucella entry into B cells, as animals with B cell receptor specificity for the irrelevant HEL antigen displayed enhanced resistance to infection and harbored fewer bacteria within B cells. Cotransfer of follicular B cells and CD4+ T cells was sufficient for enhancing susceptibility to infection, indicating follicular B cells can inhibit protective CD4+ T cell responses. Notably, the presence of B cells enhanced FoxP3 expression amongst CXCR5+ CD4+/CD44+ T cells following infection, demonstrating that B cells promote T regulatory CD4+ T cell responses during brucellosis.
    URI
    https://hdl.handle.net/10355/79461
    Degree
    Ph. D.
    Thesis Department
    Molecular microbiology and immunology (MU)
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    Access to files is limited to the University of Missouri--Columbia.
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    • 2020 MU dissertations - Access restricted to MU
    • Molecular Microbiology and Immunology electronic theses and dissertations (MU)

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