{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/274"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/274","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Cellular requirements for antibody production in a novel LPS-enhanced model of autoimmune myasthenia gravis","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.","abstract_html":"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.","abstract_has_math":false,"creators":["Windy Rose Allman"],"institution":"The University of Texas Medical Branch","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Premkumar Christadoss, M.D."],"committee_chairs":[],"committee_members":["Stephen Higgs, Ph.D.","Socrates Tzartos, Ph.D.","Silvia Pierangali, Ph.D.","Gary Klimpel, Ph.D."],"year":2009,"date_issued":"2009-07-20","date_published":"2009-07-20","updated_at":"2026-07-24T05:51:01Z","subjects":["Myasthenia Gravis","B cells","autoimmunity","antibody"],"languages":["eng"],"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."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-11302009-223210"],"render_values":[{"text":"etd-11302009-223210","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/274","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Premkumar Christadoss, M.D."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Stephen Higgs, Ph.D.","Socrates Tzartos, Ph.D.","Silvia Pierangali, Ph.D.","Gary Klimpel, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Windy Rose Allman"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2011-12-20T16:05:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2010-09-28","2011-12-20T16:05:38Z"]},{"key":"dc:date.issued","label":"Date","values":["2009-07-20"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Myasthenia Gravis","B cells","autoimmunity","antibody"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-11302009-223210"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/274"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["electronic"]},{"key":"dc:title","label":"Title","values":["Cellular requirements for antibody production in a novel LPS-enhanced model of autoimmune myasthenia gravis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Premkumar Christadoss, M.D."],"dc:contributor.committeemember":["Stephen Higgs, Ph.D.","Socrates Tzartos, Ph.D.","Silvia Pierangali, Ph.D.","Gary Klimpel, Ph.D."],"dc:creator":["Windy Rose Allman"],"dc:date.accessioned":["2011-12-20T16:05:38Z"],"dc:date.available":["2010-09-28","2011-12-20T16:05:38Z"],"dc:date.issued":["2009-07-20"],"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."],"dc:format.medium":["electronic"],"dc:identifier.other":["etd-11302009-223210"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/274"],"dc:language.iso":["eng"],"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."],"dc:subject":["Myasthenia Gravis","B cells","autoimmunity","antibody"],"dc:title":["Cellular requirements for antibody production in a novel LPS-enhanced model of autoimmune myasthenia gravis"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Texas Medical Branch"]},"updated_at":"2026-07-24T05:51:01Z"}