Effect of B cell stimulatory factor-1 (interleukin 4) on Fc epsilon and Fc gamma receptor expression on murine B lymphocytes and B cell lines.
Culture of murine splenic B cells with interleukin 4 (IL-4) caused the up-regulation of the lymphocyte Fc receptor for immunoglobulin E (IgE) (Fc epsilon R) over a similar dose range as required for Ia up-regulation. However, the expression level of the Fc receptor for immunoglobulin G (Fc gamma R) did not increase, rather IL-4 caused a slight but consistent decrease in the Fc gamma R level on the B cells. Fc epsilon R+ B hybridoma cells also responded to IL-4 by exhibiting increased Fc epsilon R expression; with the hybridoma cells Fc gamma R levels were unaffected. IL-4 caused an increase in the number of Fc epsilon R per cell and the highest levels of expression were obtained by having both IgE and IL-4 present in the culture. The specificity of the increase was demonstrated by blocking IL-4-mediated actions with monoclonal anti-IL-4 (11B11). Experiments following the incorporation of [35S]methionine into the Fc epsilon R demonstrated that IL-4 increased the rate of Fc epsilon R biosynthesis; this provides an explanation for the IL-4-induced increase in Fc epsilon R expression. IL-4, unlike IgE, had no effect on the rate of degradation of the Fc epsilon R. Interferon-gamma (IFN-gamma) totally abrogated IL-4-mediated Fc epsilon R up-regulation; at the same concentration of IFN-gamma Ia up-regulation is also suppressed, although not as effectively. IFN-gamma was shown to directly suppress Fc epsilon R synthesis, thereby explaining the inhibitory action on Fc epsilon R levels. Finally, it was shown that 11B11 inhibited the increased expression of Fc epsilon R on B cells obtained from mice during the early, but not the late, stages of Nippostrongylus brasiliensis infection. This latter finding suggests that the high Fc epsilon R levels seen early in parasite infections are dependent upon IL-4. The results overall provide further insight into the biologic activities of IL-4.
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D009349:Nematode Infections / Q000276:immunology; D009559:Nippostrongylus; D011961:Receptors, Fc / Q000096:biosynthesis*; D017455:Receptors, IgE; D017452:Receptors, IgG
D007378:Interleukins; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D015847:Interleukin-4; D007371:Interferon-gamma