Immunoglobulin superantigen protein L induces IL-4 and IL-13 secretion from human Fc epsilon RI+ cells through interaction with the kappa light chains of IgE

J Immunol. 2003 Feb 15;170(4):1854-61. doi: 10.4049/jimmunol.170.4.1854.

Abstract

Peptostreptococcus magnus protein L is a multidomain bacterial surface protein that correlates with virulence. It consists of up to five homologous Ig-binding domains (B1-B5) that interact with the variable domain of Ig kappa L chains. Intact protein L stimulates the synthesis and the release of IL-4 and IL-13 from human basophils in vitro. A protein L fragment covering the Ig-binding domains B1-B4 also induced IL-4 and IL-13 release from basophils. There was an excellent correlation (r(s) = 0.82; p < 0.001) between the maximal percent IL-4 release induced by protein L and that induced by anti-IgE and between intact protein L and the B1-B4 fragment (r(s) = 0.90; p < 0.01). Removal of IgE bound to basophils markedly reduced the IL-4 release induced by anti-IgE, protein L, and B1-B4. Preincubation of basophils with protein L or anti-IgE caused complete cross-desensitization to subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda chains) blocked anti-IgE-induced IL-4 release, but not the releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa chains) blocked both anti-IgE- and protein L-induced secretion. Cyclosporin A, but not cyclosporin H, inhibited protein L-induced release of IL-4 and IL-13 from basophils. Thus, protein L acts as a bacterial Ig superantigen to induce the synthesis and release of IL-4 and IL-13 from basophils by interacting with kappa L chains of the IgE isotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Anti-Idiotypic / metabolism
  • Antibodies, Anti-Idiotypic / physiology
  • Bacterial Proteins / physiology*
  • Basophils / drug effects
  • Basophils / immunology
  • Basophils / metabolism*
  • Basophils / microbiology
  • Binding Sites, Antibody
  • Cells, Cultured
  • Cross Reactions
  • Cyclosporine / pharmacology
  • DNA-Binding Proteins / physiology*
  • Gene Expression Regulation / immunology
  • Histamine Release / drug effects
  • Histamine Release / immunology
  • Humans
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Immunoglobulin E / physiology*
  • Immunoglobulin kappa-Chains / metabolism
  • Immunoglobulin kappa-Chains / physiology*
  • Interleukin-13 / genetics
  • Interleukin-13 / metabolism*
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism*
  • Kinetics
  • Middle Aged
  • Myeloma Proteins / metabolism
  • Peptostreptococcus / immunology
  • Peptostreptococcus / pathogenicity
  • RNA, Messenger / biosynthesis
  • Receptors, IgE / biosynthesis*
  • Repetitive Sequences, Amino Acid / immunology
  • Superantigens / physiology*

Substances

  • Antibodies, Anti-Idiotypic
  • Bacterial Proteins
  • DNA-Binding Proteins
  • Ig L-binding protein, Peptostreptococcus
  • Immunoglobulin kappa-Chains
  • Interleukin-13
  • L-protein, Peptococcus magnus
  • Myeloma Proteins
  • RNA, Messenger
  • Receptors, IgE
  • Superantigens
  • anti-IgE antibodies
  • Interleukin-4
  • Immunoglobulin E
  • Cyclosporine
  • cyclosporin H