dc.contributor.advisor | Skyberg, Jerod Alan | eng |
dc.contributor.advisor | Adamovicz, Jeffrey J. | eng |
dc.contributor.author | Dadelahi, Alexis Setareh | eng |
dc.date.issued | 2020 | eng |
dc.date.submitted | 2020 Summer | eng |
dc.description.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. | eng |
dc.description.bibref | Includes bibliographical references. | eng |
dc.format.extent | 1 online resource (xv, 172 pages) : illustrations (color) | eng |
dc.identifier.uri | https://hdl.handle.net/10355/79461 | |
dc.identifier.uri | https://doi.org/10.32469/10355/79461 | eng |
dc.language | English | eng |
dc.publisher | University of Missouri--Columbia | eng |
dc.relation.ispartofcommunity | University of Missouri--Columbia. Graduate School. Theses and Dissertations | eng |
dc.rights | Access to files is limited to the University of Missouri--Columbia. | eng |
dc.subject.other | Biology | eng |
dc.title | Investigating the deleterious role of B lymphocytes during brucella infection | eng |
dc.type | Thesis | eng |
thesis.degree.discipline | Molecular microbiology and immunology (MU) | eng |
thesis.degree.grantor | University of Missouri--Columbia | eng |
thesis.degree.level | Doctoral | eng |
thesis.degree.name | Ph. D. | eng |