IgE secretion by Epstein-Barr virus-infected purified human B lymphocytes is stimulated by interleukin 4 and suppressed by interferon gamma.
The cytokine interleukin 4 (IL-4) has been shown to induce lipopolysaccharide-activated murine B cells to differentiate into IgE-secreting cells and to stimulate IgE secretion by cultured human peripheral blood lymphoid cells. It is unclear, however, whether this effect of IL-4 on human peripheral blood lymphoid cells is a direct effect on the B cell because IL-4 can stimulate T cells and monocytes as well as B cells and does not induce purified human B cells to secrete immunoglobulin. To investigate this issue we studied the ability of IL-4 to induce IgE secretion by purified human B cells (93-96% CD20+, less than 1% CD3+) that were cultured with Epstein-Barr virus (EBV). Although B cells cultured with IL-4 alone did not secrete Ig and B cells cultured with EBV alone secreted IgM, IgG, and IgA but less than 150 pg of IgE per ml, the combination of EBV and IL-4 induced an IgE response that ranged from 11.4 to 40.3 ng/ml of culture supernatant after 26 days of culture. While IL-4 also enhanced IgM, IgG, and IgA secretion, as well as proliferation by EBV-infected B cells, these effects were less pronounced, occurred earlier during culture, and required a lower concentration of IL-4 than did the stimulation of IgE secretion. Furthermore, interferon gamma at 10 units per ml was found to inhibit IL-4/EBV-induced IgE secretion without inhibiting the other stimulatory effects of IL-4. We conclude that (i) IL-4 and interferon gamma can act directly on polyclonally activated human B cells to respectively stimulate and suppress IgE secretion and (ii) IL-4, in addition to its specific effect on IgE secretion, has a general stimulatory effect on the growth and differentiation of EBV-infected human B cells.
Thyphronitis
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Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Tsokos
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GC
June
C H
CH
Levine
A D
AD
Finkelman
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FD
D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D007376:Interleukin-2; D007377:Interleukin-3; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma