The Secondary Antigen-Specific IgE Response in Murine Lymphocytes Is Resistant to Blockade by Anti-IL4 Antibody and an Antisense Oligodeoxynucleotide for IL4 mRNA

In order to investigate the role of interleukin 4 (IL4) in the induction of antigen-specific IgE responses, we established culture conditions which allow the induction of anti-trinitrophenyl(TNP) IgE response by the coculture of TNP-keyhole limpet hemocyanin-primed C3H B cells with conalbumin (CA)-specific type 2 helper T (Th2) cell clone, D10.G4.1 in the presence of TNPCA. A maximum level of anti-TNP IgE was secreted at 1 μg/ml TNP-CA. By using filter-separated double-chamber culture plates, the physical contact between T cells and B cells was shown to be necessary in this response. Anti-TNP IgE synthesis was not significantly suppressed in the presence of 20-40 μg/ml monoclonal anti-IL4 (11B11), nor was the response further enhanced by the addition of recombinant IL4. 11B11 added together with anti-IL5 had also no suppressive effects on the IgE response. This apparent independence on IL4 might be due to the fact that IL4 is transferred from T cells to B cells in a transsynaptical way that would be refractory to the neutralization by 11B11. in order to test this possibility, we synthesized the phosphorothioate analogue of an antisense oligodeoxynucleotide against IL4 mRNA (S-oligo) for inhibiting IL4 production from Th2 cells specifically. S-oligo was effective at 10-20 μg/ml in suppressing IL4 production from D10.G4.1 cells by 80-90%. It was demonstrated that S-oligo, either alone or in combination with 11B11, did not significantly suppress anti-TNP IgE response. These results suggest that antigen-specific IgE response in primed B cells does not depend on IL4, but requires cognate interaction with Th2 cells.