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) γδ⁺, CD4⁺ and TcR αβ⁺, CD4⁺ T cell clones and interleukin (IL)‐4. The signal provided by these T cell clones was antigen nonspecific, indicating that the TcR αβ/CD3 or TcR γδ/CD3 complexes were not involved in these T‐B cell interactions. Activated TcR αβ⁺, CD8⁺, and TcR γδ⁺, CD4⁻CD8⁻, or resting CD4⁺ T cell clones were ineffective. Intact TcR αβ⁺ or TcR γδ⁺, 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 αβ⁺, CD4⁺, TcR γδ⁺, 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 αβ⁺, CD4⁺ and TcR γδ⁺, 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 αβ and TcR γδ, CD4⁺ T cells, is needed for induction of IgE production in the presence of IL‐4.

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