Differential regulation of antigen-specific IgG4 and IgE antibodies in response to recombinant filarial proteins.
Having identified two recombinant filarial proteins (Ov27 and OvD5B) that induced patient peripheral blood mononuclear cells to produce antigen-specific IgG4/IgE antibodies in vitro, we assessed the role these filarial antigens play in inducing antigen-specific isotype switching (gamma 4 and epsilon) in the absence of T cells. Purified CD19+ s gamma-/s epsilon- B cells were cultured with either of these 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 IgG4/IgE antibodies. To assess the role played by cytokines produced by B lymphocytes in antigen-driven selection of the gamma 4 or epsilon isotype, neutralizing anti-cytokine antibodies were used in vitro. While anti-IL-12 antibodies did not alter the antigen-specific IgG4/IgE production, anti-IL-6, anti-IL-13 and anti-tumor necrosis factor-alpha antibodies significantly inhibited the production of IgG4/IgE. Anti-IL-2 and anti-IL-10 antibodies appeared to down-regulate antigen-specific IgG4 antibodies without affecting antigen-specific IgE antibodies. Although anti-CD21 antibodies had no effect on specific IgE antibodies, they up-regulated specific IgG4 antibodies, a finding paralleled by anti-CD23 antibodies. These data suggest that certain filarial antigen-specific IgG4/IgE responses can be differentially regulated and that certain endogenously produced molecules from B cells-such as IL-2, IL-10, CD23 and CD21-play a significant role in the induction of specific isotypes of antigen-specific antibodies.
Garraud
O
O
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
Nkenfou
C
C
Bradley
J E
JE
Nutman
T B
TB
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity / Q000187:drug effects* / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology; D000947:Antigens, Helminth / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D005370:Filarioidea / Q000276:immunology*; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008117:Loa / Q000276:immunology; D008969:Molecular Sequence Data; D017181:Onchocerca volvulus / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology*
D000909:Antibodies, Helminth; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000947:Antigens, Helminth; D016207:Cytokines; D015801:Helminth Proteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007073:Immunoglobulin E