Differential regulation of IgG1 and IgE synthesis by interleukin 4.
IL-4/B cell stimulatory factor-1 is a T cell-derived lymphokine that has been shown to enhance IgG1 and IgE and to suppress IgG3 and IgG2b secretion by B cells stimulated with bacterial LPS. We show here that the stimulation of IgG1 and IgE secretion in response to rIL-4 is differentially regulated. The dose-response curve for IgG1 production is bimodal with peaks at 100 and 10,000 U/ml. IgE production is modest at 100 U/ml and exhibits a progressive enhancement as the IL-4 concentration is increased to 10,000 U/ml, reaching approximately 1 microgram of IgE from an initial cell number of 2 X 10(4). Both of these effects are reversed by monoclonal anti-IL-4 antibody. Neither the enhancing nor suppressing effects of IL-4 can be explained by changes in viable cell yields or [3H]thymidine incorporation. The production of both IgG1 and IgE is controlled by IL-4 in a two-phase manner. During the initial 2 d of culture with LPS, IL-4 action for both IgG1 and IgE production is relatively concentration independent at doses greater than 600 U/ml. This 2-d treatment leads to maximal IgG1 production at day 6 with no further addition of IL-4. Addition of IL-4 during the final 4 d of culture has no effect at concentrations under 100 U/ml. At higher concentrations, IL-4 is strikingly suppressive for IgG1 production. By contrast, little IgE is produced unless IL-4 is present after 2 d of culture and the response is directly dependent on the concentration of IL-4 during this second phase of culture with maximal responses observed at 10,000 U/ml. These differences in IL-4 requirements for IgG1 and IgE production, respectively, may have an important role in the regulation of the synthesis of these isotypes in responses to microbial antigens.
Snapper
C M
CM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Finkelman
F D
FD
Paul
W E
WE
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D015847:Interleukin-4; D007378:Interleukins / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007378:Interleukins; D015847:Interleukin-4; D007073:Immunoglobulin E