We have previously shown that IL-4 is an essential mediator for the synthesis of human IgE in vitro. In this study we demonstrate that prior physical contact with T cells is required by B cells to synthesize IgE in response to IL-4. Both autologous and allogeneic freshly prepared T cells were consistently able to support IL-4-dependent IgE synthesis, provided that they were added to B cells together with, or before, the addition of IL-4. In addition, most CD4+, as well as a proportion of CD8+, PHA-induced T cell clones (TCC) established from two HLA-DR incompatible donors, supported, in the presence of exogenous IL-4, the synthesis of IgE in B cells from the majority of individuals tested including both donors of cloned T cells. An alloreactive TCC able to produce IL-4 in response to HLA-DR4+ B cells and to induce HLA-DR4+ B cells to synthesize IgE, acquired the ability to support IgE synthesis by B cells lacking the appropriate alloantigen provided that exogenous IL-4 was added. Although the ability of freshly prepared T cells to support IgE synthesis was consistently abrogated by fixation with paraformaldehyde (PF), such a treatment variably affected the IgE-inducing ability of TCC. Preactivation with anti-CD3 before treatment with PF maintained or even enhanced the ability of TCC to support IL-4-dependent IgE synthesis. More importantly, preactivation with anti-CD3, followed by fixation with PF, enabled TCC, apparently devoid of IgE-inducing activity in unfixed condition, to support IL-4-dependent IgE synthesis. Taken together these data suggest that at least two signals are involved in the triggering of human B cells to IgE production: the first is delivered by a T-B cell contact and the second by IL-4. The physical signal delivered by T cells does not necessarily consist of cognate interaction. Non-cognate contact-dependent induction of B cells to IgE synthesis in response to IL-4 appears to be related to molecule(s) distinct from the TCR/CD3 complex, but fully expressed on the membrane of TCR/CD3-activated T cells.

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