dc.creator | Williams, Jonathan Murphy | |
dc.date.accessioned | 2020-08-23T15:43:35Z | |
dc.date.available | 2016-11-09 | |
dc.date.issued | 2015-11-09 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-11092015-092347 | |
dc.identifier.uri | http://hdl.handle.net/1803/14475 | |
dc.description.abstract | Overall, these studies examine how peripheral tolerance is governed for autoreactive B lymphocytes that bind the relevant autoAg, insulin. CSR-competent anti-insulin B cells enter mature compartments but are anergic, demonstrated by impaired proliferation to stimulation by a panel of B cell mitogens in vitro and total lack of IgG anti-insulin antibody production following TD immunization of VH125SD B6 mice. Reversal of anti-insulin B cell anergy is demonstrated by proliferation to insulin plus LPS in vitro and IgG2a antibody production following immunization of VH125SD mice with insulin conjugated to a type 1 TI antigen. This combined BCR/TLR co-stimulation effect in vivo is accompanied by entry of insulin-binding B cells into GCs, in contrast to expectations that such TI-mediated responses would arise in extrafollicular sites. In GCs, anti-insulin L chains are not discarded but rather selected from the pre-immune repertoire. These studies reveal a new pathway to drive loss of tolerance for CSR-competent anti-insulin B cells. | |
dc.format.mimetype | application/pdf | |
dc.subject | Autoimmunity | |
dc.subject | Tolerance | |
dc.subject | B cells | |
dc.subject | Insulin | |
dc.subject | Type 1 Diabetes | |
dc.title | Peripheral Tolerance in Anti-Insulin B Lymphocytes | |
dc.type | dissertation | |
dc.contributor.committeeMember | Luc Van Kaer | |
dc.contributor.committeeMember | Eric Sebzda | |
dc.contributor.committeeMember | Maureen Gannon | |
dc.contributor.committeeMember | James W. Thomas | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Microbiology and Immunology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2016-11-09 | |
local.embargo.lift | 2016-11-09 | |
dc.contributor.committeeChair | Mark Boothby | |