Cellular requirements for antibody production in a novel LPS-enhanced model of autoimmune myasthenia gravis
| dc.contributor.advisor | Premkumar Christadoss, M.D. | en_US |
| dc.contributor.committeeMember | Stephen Higgs, Ph.D. | en_US |
| dc.contributor.committeeMember | Socrates Tzartos, Ph.D. | en_US |
| dc.contributor.committeeMember | Silvia Pierangali, Ph.D. | en_US |
| dc.contributor.committeeMember | Gary Klimpel, Ph.D. | en_US |
| dc.creator | Windy Rose Allman | en_US |
| dc.date.accessioned | 2011-12-20T16:05:38Z | |
| dc.date.available | 2010-09-28 | en_US |
| dc.date.available | 2011-12-20T16:05:38Z | |
| dc.date.created | 2009-11-30 | en_US |
| dc.date.issued | 2009-07-20 | en_US |
| dc.description.abstract | Bacterial lipopolysaccharide (LPS) is a T cell-independent adjuvant known to abrogate peripheral tolerance. For the first time, the potential of LPS to induce antigenspecific B cell responses to acetylcholine receptor (AChR) in myasthenia gravis (MG) was evaluated in wild type (WT), CD4-/-, and CD8-/- C57BL/6 mice. Historically, MG\r\nhas been induced in mice by immunization with AChR emulsified in complete Freund’s\r\nadjuvant (CFA). WT mice immunized with AChR in LPS developed an MG-like disease\r\n(LPS-EAMG) similar to a disease induced by immunization with AChR in complete\r\nFreund’s adjuvant (CFA-EAMG). The CD4-/- mice were resistant to the development of\r\nCFA-EAMG, but had significantly higher frequencies of IgG expressing AChR-binding\r\nB cells than WT mice. However, CFA-AChR immunization of CD4-/- mice failed to\r\ndifferentiate these cells to secrete anti-AChR IgG. The CD4-/- mice were susceptible to\r\nthe development of LPS-EAMG and also had significantly higher frequencies of IgG\r\nexpressing AChR-binding B cells than WT mice. WT and CD4-/- mice in the LPSEAMG\r\nmodel had significant amounts of secreted high-affinity anti-AChR IgG2,\r\nimmune complex deposits (IgG, C3, MAC) in muscle, and elevated sera levels of the Bcell survival factor, BAFF. Our results indicate that LPS abrogated B cell differentiation\r\nto antibody secreting cells in the LPS-EAMG model. Furthermore, CD8-/- mice were\r\nalso susceptible to the development of LPS-EAMG, but were resistant to the development of moderate or severe signs of EAMG. While CD8 deficiency did not affect the quantity or avidity of secreted anti-AChR antibodies, it significantly reduced the\r\nsurvival of circulating IgG expressing AChR-binding B cells. The findings, accordingly\r\nhave allowed us to identify an alternate cellular mechanism for the development of EAMG. | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-11302009-223210 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/274 | |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. | en_US |
| dc.subject | Myasthenia Gravis | en_US |
| dc.subject | B cells | en_US |
| dc.subject | autoimmunity | en_US |
| dc.subject | antibody | en_US |
| dc.title | Cellular requirements for antibody production in a novel LPS-enhanced model of autoimmune myasthenia gravis | en_US |
| dc.type.genre | dissertation | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Microbiology and Immunology | en_US |
| thesis.degree.grantor | The University of Texas Medical Branch | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | PhD | en_US |