Soluble CD23 containing B cell supernatants induce IgE from peripheral blood B-lymphocytes 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 epsilon R (Fc epsilon 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.
Department of Medicine, University of California-Los Angeles School of Medicine 90024.
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Saxon
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Bahati
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Stevens
D000328:Adult; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis* / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D019002:CD56 Antigen; D002478:Cells, Cultured; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008875:Middle Aged; D011961:Receptors, Fc / Q000032:analysis* / Q000502:physiology; D017455:Receptors, IgE
D000944:Antigens, Differentiation, B-Lymphocyte; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D011961:Receptors, Fc; D017455:Receptors, IgE; D015847:Interleukin-4; D007073:Immunoglobulin E