Interleukin-4 induces both IgG4 and IgE secretion by peripheral blood B cells.
Peripheral blood mononuclear cells (PBMCs) from healthy nonallergic donors were cultured with recombinant interleukin-4 (rIL-4), and the Ig of different isotypes was quantitated in the culture supernatants by radioimmunoassays. Recombinant IL-4 induced IgG4 and IgE secretion in a dose-dependent manner, whereas it had no consistent effect on the secretion of the other isotypes. In the absence of rIL-4, B cells in the PBMC preparations secreted less than 1 ng IgE/ml and a mean of 5 ng IgG4/ml. In the presence of the optimal dose of 100 U rIL-4/ml, PBMCs from five donors secreted a mean +/- SEM of 37 +/- 8 ng IgE/ml and 66 +/- 25 ng IgG4/ml. In kinetic studies, no IgG4 or IgE secretion was detected during the first 5 days of culture, and approximately 50% of the IgG4 and IgE secreted by day 15 was detected in supernatants on day 7. Cycloheximide, actinomycin-D, and mytomycin-C completely inhibited the rIL-4-induced IgG4 and IgE secretion, indicating that de novo protein, RNA, and DNA synthesis was required. As shown by Percoll buoyant density centrifugation, rIL-4 induced B cells in the high-density fraction to secrete IgG4 and IgE, whereas it inhibited spontaneous IgG4 secretion by low-density B cells. Interferon-gamma inhibited IL-4-induced IgG4 and IgE secretion. The data demonstrate that IL-4 induces small, dense, peripheral blood B cells to secrete not only IgE but also IgG4, which parallells the IL-4-induced IgE and IgG1 secretion by murine B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Nüsslein
H G
HG
Research Institute of Scripps Clinic, La Jolla, California.
Spiegelberg
H L
HL
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism*; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma