Characterization of human IgA-inducing protein
| dc.contributor.advisor | D. Mark Estes, Ph.D. | en_US |
| dc.contributor.committeeMember | Victor E. Reyes, Ph.D. | en_US |
| dc.contributor.committeeMember | Randall M. Goldblum, M.D. | en_US |
| dc.contributor.committeeMember | Marcus Kehrli, D.V.M., Ph.D. | en_US |
| dc.contributor.committeeMember | Alfredo G. Torres, Ph.D. | en_US |
| dc.creator | Mark Allen Endsley | en_US |
| dc.date.accessioned | 2011-12-20T16:04:31Z | |
| dc.date.accessioned | 2014-02-19T22:05:01Z | |
| dc.date.available | 2010-09-28 | en_US |
| dc.date.available | 2011-12-20T16:04:31Z | |
| dc.date.available | 2014-02-19T22:05:01Z | |
| dc.date.created | 2009-03-30 | en_US |
| dc.date.issued | 2009-03-12 | en_US |
| dc.description.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. | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-03302009-092938 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/78 | |
| 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 | mucosa | en_US |
| dc.title | Characterization of human IgA-inducing protein | 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 |