[-] Show simple item record

dc.contributor.advisorSkyberg, Jerod Alaneng
dc.contributor.advisorAdamovicz, Jeffrey J.eng
dc.contributor.authorDadelahi, Alexis Setareheng
dc.date.issued2020eng
dc.date.submitted2020 Summereng
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.bibrefIncludes bibliographical references.eng
dc.format.extent1 online resource (xv, 172 pages) ; Illustrationseng
dc.identifier.urihttps://hdl.handle.net/10355/79461
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsAccess to files is limited to the University of Missouri--Columbia.eng
dc.subject.otherBiologyeng
dc.titleInvestigating the deleterious role of B lymphocytes during brucella infectioneng
dc.typeThesiseng
thesis.degree.disciplineMolecular microbiology and immunology (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


Files in this item

[PDF]

This item appears in the following Collection(s)

[-] Show simple item record