Independent regulation of interleukin 4 (IL-4)-induced expression of human B cell surface CD23 and IgM: functional evidence for two IL-4 receptors.
Activation of human B cells with interleukin 4 (IL-4) is known to result in increased expression of CD23 (the low-affinity receptor for IgE) and sIgM. However, whereas CD23 expression is increased by several B cell mitogens, including phorbol 12-myristate 13-acetate, Epstein-Barr virus, anti-immunoglobulin (Ig), and IL-4, surface IgM (sIgM) expression is increased only with IL-4, suggesting that expression of each surface antigen is regulated independently. This was confirmed in three different ways. First, in dose-response experiments, it was shown that 10 times the concentration of IL-4 was required for CD23 than for sIgM expression. Similar or even higher concentrations of IL-4 were required for proliferation. In fact, optimal sIgM expression was obtained in some experiments with concentrations of IL-4 (1-5 units/ml) which had little or no effect on either CD23 expression or B cell proliferation. Secondly, IL-4 is known to activate the phosphatidyl inositol pathway in human B cells followed 8-10 min later by an increase in cAMP. Pharmacologically mimicking this pathway by brief exposure of resting B cells to phorbol dibutyrate plus ionomycin followed 10 min later with dibutyryl cAMP resulted in an increase in expression of CD23 but not sIgM. Thirdly, CD19 monoclonal antibody, which inhibits B cell proliferation in response to IL-4 plus anti-Ig, was found to inhibit IL-4-induced CD23 but not sIgM expression. These results show that CD23 and sIgM expression are regulated independently and are consistent with the existence of two separate signal transduction pathways stimulated by IL-4, which may be coupled to distinct IL-4 receptors.
Rigley
K P
KP
Department of Immunology, Institute of Child Health, London, UK.
Thurstan
S M
SM
Callard
R E
RE
D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism* / Q000494:pharmacology; D000954:Antigens, Surface / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D007075:Immunoglobulin M; D011961:Receptors, Fc; D017455:Receptors, IgE; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4; D015240:Phorbol 12,13-Dibutyrate; D015759:Ionomycin