SOLUBLE CD23 CONTAINING-B CELL SUPERNATANTS INDUCE IGE FROM PERIPHERAL-BLOOD LYMPHOCYTES-B AND COSTIMULATE WITH INTERLEUKIN-4 IN INDUCTION OF IGE

The role of soluble fragments of CD23 and their relationship to interleukin-4 (IL-4) in the in vitro production of IgE by normal human peripheral blood mononuclear cells was examined. Most donors' cells were induced to produce IgE in vitro by IL-4 during a 9- to 21-day culture. This stimulation was not observed in the absence of T cells. Inability of IL-4 to induce IgE in nonresponding cultures was associated with a failure to express CD23 on Lev-19+ natural killer cells; CD23 expression on B cells and monocytes was equivalent in responding and nonresponding subjects. Concentrated supernatants from Epstein-Barr virus-transformed B cell lines containing soluble fragments (sCD23) of the low-affinity Fc∈R (Fc∈R-II, CD23) induced IgE from all donors' cells in the absence of T cells. The sCD23 containing supernatants were demonstrated to be devoid of IL-4, and their effect could not be abrogated by anti-IL-4. IgE induction by both IL-4 and sCD23-containing supernatant were blocked by anti-CD23 monoclonal antibody. Affinity absorption of sCD23 removed the IgE-inducing activity. The cells most responsive to the sCD23 material were small resting B cells rather than large in vivo activated cells. IL-4 synergized with sCD23-containing supernatant in the T cell-depleted cultures, and limiting dilution analyses demonstrated that IL-4 caused a more than tenfold increase in the precursor frequency of cells capable of responding to sCD23-containing supernatant with IgE production. These data are consistent with the hypothesis that IL-4 has multiple effects in the ultimate induction of human IgE including (1) commitment of B cells to IgE and (2) the generation of natural killer cell sCD23 fragments that subsequently drive IgE-committed cells to IgE synthesis. © 1990 Mosby-Year Book, Inc.