Open AccessInhibition of IL‐4 receptor up‐regulation on B cells by antisense oligodeoxynucleotide suppresses IL‐4‐induced human IgE production
Author(s) -
IKIZAWA K.,
KAJIWARA K.,
KOSHIO T.,
MATSUURA N.,
YANAGIHARA Y.
Publication year - 1995
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1111/j.1365-2249.1995.tb03710.x
Subject(s) - immunoglobulin e , immunology , receptor , biology , interleukin 4 , antibody , chemistry , microbiology and biotechnology , cytokine , biochemistry
SUMMARY IL‐4 is shown to up‐regulate its own receptor (IL‐4R) on human lymphocytes, but the functional significance of up‐regulated IL‐4R is not clear regarding IgE production. This study investigated the possible role of IL‐4‐induced up‐regulation of IL‐4R on B cells in the induction of human Ig–E synthesis by means of antisense strategy. Among three antisense oligodeoxynucleotides designed against the downstream of translation initiation site of 1L‐4R cDNA. S‐oligo 1, complementary to nucleotide 1‐24, showed the strongest inhibition of the constitutive expression of IL‐4R on Daudi cells. Addition of S‐oligo 1 together with IL‐4 also decreased the up‐regulated but not constitutive levels of IL‐4R on peripheral blood B cells without affecting the concomitant enhancement of CD23, CD40, HLA‐DR and surface IgM expression, indicating that its effect is specific for IL‐4R up‐regulation. When S‐oligo 1 was added to B cells costimulated with IL‐4 and anti‐CD40 MoAb, it induced a dose‐dependent inhibition of IgE production. This inhibition was accompanied by a decrease in the expression of mature C transcripts, whereas the accumulation of germ‐line C E transcripts was not affected by S‐oligo 1. These data suggest that the signal transduction mediated by the up‐regulated IL‐4R on B cells may be intimately associated with the induction of isotype switching to IgE that leads to mature C transcription and IgE production.