Induction of IgE synthesis in normal human B cells. Sequential requirements for activation by an alloreactive T cell clone and IgE-potentiating factors.

Abstract

Two human alloreactive T cell clones were established from a one-way mixed lymphocyte culture involving two nonatopic donors, and were assessed for their capacity to induce IgE synthesis by B cells obtained from the original stimulator. The two alloreactive T cell clones studied induced IgG but not IgE synthesis in normal B cells. However, one of the two clones, clone 2H6, induced IgE synthesis in the presence of supernatants from T cell lines derived from patients with the hyper-IgE syndrome (HIE), and enriched for T cells bearing receptors for IgE. These supernatants by themselves caused no IgE synthesis in nonatopic B cells. The potentiating factors in these supernatants were shown to bind to IgE. Time sequence experiments indicated that interaction of the B cells with the alloreactive clone 2H6 renders them responsive to the action of the IgE-potentiating factors. These results indicate that induction of IgE synthesis in normal B cells involves at least two sequential T cell derived signals. Furthermore, T cell clones are heterogenous in their capacity to provide these signals.

Induction of IgE Synthesis in Anti-IgM-Activated Nonatopic Human B Cells by Recombinant Interleukin-3

“…In support of this hypothesis is the following observation. T cell clones established by Umetsu et al [1] and Leung et al [2] required more than one soluble factor (IgE-binding factor) from IgE-Fc-receptor-bearing T cell lines to induce IgE synthesis by nonatopic B cells.…”

“…However, re cent studies by Umetsu et al [1], Leung et al [2], Sherr et al [3] and Ricci et al [4] have shown that either T cell clones or soluble products from atopic T cells are capable of inducing IgE synthesis selectively in sub populations of nonatopic B cells. In addition, recent studies by Snapper et al [5] indicate that interleukin-4 (IL-4) selectively augments IgE and IgG 1 synthesis by murine B cells, and Del Prete et al [6] showed that re combinant induces IgE synthesis in B cells from both atopic and nonatopic donors.…”

IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2.

“…However, various studies have shown that cocultivation of alloreactive and autoreactive T-cell clones with peripheral blood B cells resulted not only in IgE production but also in IgG and IgM production (11)(12)(13). IgE production could also be induced by T-cell clones activated by phytohemagglutinin or anti-CD3 monoclonal antibodies (mAbs) in the apparent absence of specific interaction with highly purified tonsil B cells (14).…”

Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma.

“…Regulatory T cells that selectively enhance (4)(5)(6)(7)(8)(9)(10) or suppress (11,12) IgE responses in humans have been identified. Products of regulatory T cells that suppress or enhance IgE production have also been described.…”