IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2.
The effect of human recombinant interleukin 4 (IL-4) on antibody production by normal peripheral blood mononuclear cells enriched for B cells was investigated. IL-4 preferentially induced IgE synthesis in vitro. In addition, a low induction of IgG production was observed, whereas IL-4 had no effect on IgA and IgM synthesis. The IL-4-induced IgE production by B cells required T cells and monocytes but was specifically inhibited by an anti-IL-4 antiserum indicating that, although IL-4 acts indirectly, it is responsible for the induction of IgE synthesis. IL-4-induced IgE production was blocked in a dose-dependent way by interferon gamma (IFN-gamma), interferon alpha (IFN-alpha), and prostaglandin E2. IFN-gamma also inhibited IL-4-induced IgG production. These inhibitory effects of IFN-gamma and IFN-alpha on IgE production cannot be attributed to toxic effects since IFN-alpha induced IgM production in the presence of IL-4, whereas IFN-gamma was ineffective in inhibiting IgG production induced by IL-2. IFN-gamma, IFN-alpha, and prostaglandin E2 also inhibited IL-4-induced expression of the low-affinity receptor for the Fc portion of IgE (CD23) on B cells, indicating that there is an association between CD23 expression and IL-4-induced IgE production. This theory was supported by the finding that IL-4-induced IgE production was inhibited by F(ab')2 fragments of an anti-CD23 monoclonal antibody.
Pène
J
J
UNICET, Laboratory for Immunological Research, Dardilly, France.
Rousset
F
F
Brière
F
F
Chrétien
I
I
Bonnefoy
J Y
JY
Spits
H
H
Yokota
T
T
Arai
N
N
Arai
K
K
Banchereau
J
J
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D002478:Cells, Cultured; D015232:Dinoprostone; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008214:Lymphocytes / Q000276:immunology*; D011458:Prostaglandins E / Q000494:pharmacology*; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000944:Antigens, Differentiation, B-Lymphocyte; D007370:Interferon Type I; D007378:Interleukins; D011458:Prostaglandins E; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D015232:Dinoprostone