Rapid polarization of Th2 cells during induction of antigen-specific IgE antibodies in vitro

Background Type 2 T-helper cells (Th2) are involved in the regulation of th e humoral immune response against antigens and allergens and directly affec t which isotype will be produced. The mechanism that regulates antigen-spec ific IgE secretion and immune deviation is still not known. Objectives To delineate mechanisms behind antigen-specific IgE secretion we have used in vitro immunization and focused on T-cell phenotype and the ac tivation status of the transcription factor NF kappa B. Methods Peripheral blood lymphocytes (PBMC) from seronegative donors were i mmunized in vitro with a peptide consisting of both a T-cell and a B-cell e pitope. Results Antigen-specific IgE antibodies could be detected after a primary i mmunization, during which T-helper cells secreted type 2 cytokines. Specifi c IgE was also detected in the secondary immunization, but due to a rapid p olarization from Th2 to Th1 phenotype, exogenous IL-4 was required for the specific IgE secretion. Analysis of NF kappa B activation in B and T cells during primary and secondary immunization showed that NF kappa B could be d etected in both B and T cells during primary immunization, but was dependen t on exogenous IL-4 in the secondary immunization. Conclusion This is the first evidence of antigen-specific IgE induction in vit ro using naive B cells, demonstrating the involvement of T-helper cell phenotype and NF kappa B and demonstrates the usefulness of in vitro cultur es to study the effect of antigens on human immunocytes.