Characterization of human IgA-inducing protein

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Title: Characterization of human IgA-inducing protein
Author: Mark Allen Endsley
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 - & #945 ; 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 .
URI: http : / /hdl .handle .net /2152 .3 /78
Date: 2009-03-12


Characterization of human IgA-inducing protein. Doctoral dissertation, The University of Texas Medical Branch. Available electronically from http : / /hdl .handle .net /2152 .3 /78 .

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