MEMBRANES OF ACTIVATED CD4+ T-CELLS EXPRESSING T-CELL RECEPTOR (TCR) ALPHA-BETA OR TCR GAMMA-DELTA INDUCE IGE SYNTHESIS BY HUMAN B-CELLS IN THE PRESENCE OF INTERLEUKIN-4

In the present study it is demonstrated that human B cells can be induced to switch to IgE production following a contact-mediated signal provided by activated T cell receptor (TcR) gamma-delta+, CD4+ and TcR alpha-beta+, CD4+ T cell clones and interleukin (IL)-4. The signal provided by these T cell clones was antigen nonspecific, indicating that the TcR alpha-beta/CD3 or TcR gamma-delta/CD3 complexes were not involved in these T-B cell interactions. Activated TcR alpha-beta+, CD8+, and TcR gamma-delta+, CD4-CD8-, or resting CD4+ T cell clones were ineffective. Intact TcR alpha-beta+ or TcR gamma-delta+, CD4+ T cell clones could be replaced by plasma membrane-enriched fractions isolated from these activated CD4+ T cell clones. In contrast, membranes isolated from resting TcR alpha-beta+, CD4+, TcR gamma-delta+, CD4+ T cell clones or an Epstein-Barr virus (EBV)-transformed B cell line (EBV-LCL) failed to provide the costimulatory signal that, in addition to IL-4, is required for induction of IgE synthesis. As described for intact CD4+ T cells, CD4+ T cell membranes induced purified surface IgM+ B cells to switch to IgG4- and IgE- but not to IgA- producing cells, excluding the possibility of a preferential outgrowth of IgG4- and IgE-committed B cells. The membrane activity was inhibited by protease or heat treatment. Induction of IgE synthesis by B cells co-cultured with both TcR alpha-beta+, CD4+ and TcR gamma-delta+, CD4+ T cell clones and membrane preparations of these cells was blocked by anti-class II major histocompatibility complex (MHC) monoclonal antibodies (mAb), whereas various anti-CD4 mAb had differential blocking effects. Murine L cells, or EBV-LCL transfected with CD4 could not replace CD4+ T cell clones. These results indicate that, although CD4 and class II MHC antigens are required for productive CD4+ T cell clone-B cell interactions, an additional signal, provided by a membrane associated (glyco) protein that is induced by activation of both TcR alpha-beta and TcR gamma-delta, CD4+ T cells, is needed for induction of IgE production in the presence of IL-4.