Stimulation of IgG production by glucocorticoids in human myeloma lymphoblasts.
LICR-LON-HMy2 cells (HMy2 cells), an established line of human myeloma lymphoblasts, produce and secrete IgG, and have been used for production of human-human hybridomas. We have previously shown that HMy2 cells are growth-inhibited by glucocorticoids and contain high affinity, saturable, steroid-specific glucocorticoid receptors. Here we report that treatment for 0-4 days with the synthetic glucocorticoid dexamethasone (1,4-pregnadien-9-fluoro-16 alpha-methyl-11 beta,17 alpha,21-triol-3,20-dione) leads to time-dependent increases in IgG secretion rates as measured by goat anti-human IgG antibodies in an enzyme-linked immunosorbent assay. Stimulation of IgG secretion is dependent on the concentration of dexamethasone employed, with half-maximal stimulation occurring between 1.10(-9) and 1.10(-8) M, and maximal stimulation occurring at 1.10(-7) M. Stimulation of IgG secretion is specific for active glucocorticoids such as cortisol and dexamethasone; treatment of cells with 17 beta-estradiol, progesterone, dihydrotestosterone, and aldosterone has little, if any, effect on IgG secretion. Finally, dexamethasone markedly stimulates both secreted and newly synthesized IgG, as determined by continuous and pulse labeling of extracellular and intracellular proteins, respectively, followed by binding to protein A-Sepharose, gel electrophoresis, and autoradiography. Thus, although dexamethasone effects on post-translational or secretory processes have not been ruled out, our data indicate that increased biosynthesis of IgG accounts for most, if not all, of the observed increase in IgG secretion rates. In summary our results demonstrate that despite the known immunosuppressive effects of glucocorticoids, these hormones can stimulate IgG biosynthesis and secretion in human myeloma lymphoblasts in vitro.
Manzer
D S
DS
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT 06510.
Littlefield
B A
BA
D000921:Antibody-Producing Cells / Q000187:drug effects*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006825:Hybridomas / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000378:metabolism; D009194:Myeloma Proteins / Q000096:biosynthesis*; D012636:Secretory Rate / Q000187:drug effects; D013256:Steroids / Q000494:pharmacology
D007074:Immunoglobulin G; D009194:Myeloma Proteins; D013256:Steroids; D003907:Dexamethasone