{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/78"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/78","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Characterization of human IgA-inducing protein","abstract":"Over the last several years there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as BAFF and APRIL have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). Here we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naïve B cells in vitro. Monocyte derived DCs were cultured in vitro with TLR agonists (3,4,5, and 9), other factors including CD40L, GM-CSF, and IL-4, and the neuropeptide vasoactive intestinal peptide (VIP). Under in vitro stimulation with VIP and CD40L, IGIP mRNA expression was up-regulated as much as thirty five-fold above non-stimulated samples within 12-48 hours. Naïve B cells cultured with exogenous rhIGIP produced IgA in significantly greater quantities than non-stimulated controls, and I demonstrated that IGIP stimulation drives the production of µ-α switch circles from IgM+/IgD+ naïve human B cells, indicating its role as an IgA switch factor. Additionally, the capacity of IGIP to elicit a mucosal IgA response was evaluated as part of a vaccine preparation, using a putative HIV-1 vaccine in a SCID-hu mouse model. SCID-hu mice were immunized with a dextran-based HIV-1 vaccine carrying gp120, with or without IGIP, and both serum and mucosal antibody responses were measured. While protection was sporadic, robust antibody responses were detected at both locations.","abstract_html":"Over the last several years there has been a great deal of progress in characterizing the role of dendritic cells (DCs) in the activation and modulation of B cells. DC-secreted chemokines can induce B cell trafficking to the lymph nodes. DC-produced survival factors such as BAFF and APRIL have been shown to be essential for B cell maturation, but have also been implicated in class-switch recombination and B cell lymphoma survival. Recently added to this list of DC-derived factors effecting B cells is IgA-inducing protein (IGIP). Here we characterize production of IGIP by human DCs, and examine its capacity to induce IgA class switching and differentiation of naïve B cells in vitro. Monocyte derived DCs were cultured in vitro with TLR agonists (3,4,5, and 9), other factors including CD40L, GM-CSF, and IL-4, and the neuropeptide vasoactive intestinal peptide (VIP). Under in vitro stimulation with VIP and CD40L, IGIP mRNA expression was up-regulated as much as thirty five-fold above non-stimulated samples within 12-48 hours. Naïve B cells cultured with exogenous rhIGIP produced IgA in significantly greater quantities than non-stimulated controls, and I demonstrated that IGIP stimulation drives the production of µ-α switch circles from IgM+/IgD+ naïve human B cells, indicating its role as an IgA switch factor. Additionally, the capacity of IGIP to elicit a mucosal IgA response was evaluated as part of a vaccine preparation, using a putative HIV-1 vaccine in a SCID-hu mouse model. SCID-hu mice were immunized with a dextran-based HIV-1 vaccine carrying gp120, with or without IGIP, and both serum and mucosal antibody responses were measured. While protection was sporadic, robust antibody responses were detected at both locations.","abstract_has_math":false,"creators":["Mark Allen Endsley"],"institution":"The University of Texas Medical Branch","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["D. Mark Estes, Ph.D."],"committee_chairs":[],"committee_members":["Victor E. Reyes, Ph.D.","Randall M. Goldblum, M.D.","Marcus Kehrli, D.V.M., Ph.D.","Alfredo G. Torres, Ph.D."],"year":2009,"date_issued":"2009-03-12","date_published":"2009-03-12","updated_at":"2026-07-24T05:50:51Z","subjects":["mucosa"],"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-03302009-092938"],"render_values":[{"text":"etd-03302009-092938","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/78","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["D. Mark Estes, Ph.D."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Victor E. Reyes, Ph.D.","Randall M. Goldblum, M.D.","Marcus Kehrli, D.V.M., Ph.D.","Alfredo G. 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