Antigen-specific CD4+ T-B cell interplay induces a robust, polyreactive systemic immunoglobulin response to commensal bacteremia.

Simple item page
dc.contributor.advisorGeuking, Markus B.
dc.contributor.authorKoegler, Mia Elizabeth
dc.contributor.committeememberPeters, Nathan C.
dc.contributor.committeememberHirota, Simon Andrew
dc.contributor.committeememberJenne, Craig N.
dc.date2020-06
dc.date.accessioned2020-03-06T17:33:02Z
dc.date.available2020-03-06T17:33:02Z
dc.date.issued2020-03-04
dc.description.abstractThe impact of cognate CD4+ T cell help on the systemic antibody response during commensal bacteremia was assessed in detail in this thesis. To specifically evaluate cognate T cell-B cell interactions, we utilized a genetically modified commensal E. coli strain that expressed gp61, an additional T helper epitope, in its outer membrane ompC protein (E. coli ompC_gp61). Germ-free mice that were systemically primed with E. coli ompC_gp61 produced a significantly more robust E. coli-specific antibody response than mice that received the corresponding wild-type (WT) E. coli strain. The observed antibody response to E. coli ompC_gp61 appeared to be MHC II haplotype-dependent, as this phenomenon was reproducible in C57BL/6 mice (I-Ab) but not in BALB/c mice (I-Ad and I-Ed). Furthermore, mice adoptively transferred with gp61-specific SMARTA CD4+ T cells and later challenged with E. coli ompC_gp61 produced significantly more E. coli-specific IgM than recipient mice that were primed with WT E. coli. This finding suggests that the proportion of antigen-specific CD4+ T cells present during systemic immune priming may impact on class switch recombination and IgM+ memory formation. Finally, increasing gut microbiota complexity resulted in lower E. coli-specific antibody titers compared to germ-free mice in response to E. coli ompC_gp61 priming. However, non-primed mice with a more complex gut microbiota had higher total serum antibodies than their germ-free counterparts. Collectively, these data suggest that cognate CD4+ T cell help during commensal-induced bacteremia can orchestrate a potent, commensal-specific, and polyreactive antibody response. These findings shed new light on the systemic humoral immune response to bacteremia and could potentially be exploited to develop more effective and personalized vaccine strategies.en_US
dc.identifier.citationKoegler, M. E. (2020). Antigen-specific CD4+ T-B cell interplay induces a robust, polyreactive systemic immunoglobulin response to commensal bacteremia. (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/37629
dc.identifier.urihttp://hdl.handle.net/1880/111719
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectInfectionen_US
dc.subjectAntibodiesen_US
dc.subjectMicrobiotaen_US
dc.subject.classificationMicrobiologyen_US
dc.subject.classificationImmunologyen_US
dc.titleAntigen-specific CD4+ T-B cell interplay induces a robust, polyreactive systemic immunoglobulin response to commensal bacteremia.en_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Immunologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
Files
Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
ucalgary_2020_koegler_mia.pdf
Size:
22.49 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
2.62 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Open Theses and Dissertations