Differential regulation of antigen-specific IgG4 and IgE antibodies in response to recombinant filarial proteins |
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Authors: | Garraud Olivier; Nkenfou Celine; Bradley Janette E; Nutman Thomas B |
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Institution: | 1 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 9000 Rockville Pike, Building 4, Room 126, Bethesda, MD 20892, USA
2 New England Biolabs Beverly, MA 01915, USA
3 Salford Universite Salford M5 4WT, UK |
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Abstract: | Having identified two recombinant filarial proteins (Ov27 andOvD5B) that induced patient peripheral blood mononuclear cellsto produce antigen-specific lgG4/lgE antibodies in vitro, weassessed the role these filarial antigens play in inducing antigen-specificisotype switching ( 4 and iv) in the absence of T cells. PurifiedCD19+ s –/s – B cells were cultured with either ofthese antigens in the presence of anti-CD40 mAb and human IL-4.Both antigen and polyclonal signals delivered by IL-4 (or IL-13)were necessary for the induction of specific lgG4/lgE antibodies.To assess the role played by cytokines produced by B lymphocytesin antigen-driven selection of the 4 or isotype, neutralizinganti-cytokine antibodies were used in vitro. While anti-IL-12antibodies did not alter the antigen-specific lgG4/lgE production,anti-IL-6, anti-IL-13 and anti-tumor necrosis factor- antibodiessignificantly inhibited the production of lgG4/lgE. Anti-IL-2and anti-IL-10 antibodies appeared to down-regulate antigen-specificlgG4 antibodies without affecting antigen-specific IgE antibodies.Although anti-CD21 antibodies had no effect on specific IgEantibodies, they up-regulated specific lgG4 antibodies, a findingparalleled by anti-CD23 antibodies. These data suggest thatcertain filarial antigen-specific lgG4/lgE responses can bedifferentially regulated and that certain endogenously producedmolecules from B cells—such as IL-2, IL-10, CD23 and CD21–playa significant role in the induction of specific isotypes ofantigen-specific antibodies. |
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Keywords: | anti-CD40 B cells filarial IgE IgG4 sotypes |
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