title: Induction of human IgE synthesis in B cells by a basophilic cell line, KU812.
abstract: Induction of human IgE synthesis in B cells requires, in addition to IL-4 or IL-13, a second signal provided by CD40 ligand (CD40L) on activated Th2-type CD4+ T cells that do not or weakly express Fas ligand (FasL). Mast cells and basophils also produce IL-4 or IL-13 and express CD40L after immunologic or pharmacologic stimulation, although it is unknown whether these cells express FasL. This study investigated the capacity of KU812 cells, a human basophilic cell line, to produce IL-4 and IL-13, to express CD40L and FasL, and to induce IgE and IgG4 synthesis in human normal B cells. Upon stimulation of KU812 cells with either phorbol myristate acetate (PMA) or ionomycin (Iono), IL-4, but not IL-13, was produced in response to Iono, while IL-13, but not IL-4, was inducible by PMA. Moreover, both the time courses of IL-4 and IL-13 production and their amounts secreted were different; IL-4 production was transient, IL-13 production gradually increased, and IL-13 was heavily secreted as compared with IL-4. The combination of PMA and Iono (PMA/Iono) induced higher production of IL-4 or IL-13 than did Iono or PMA alone. KU812 cell-derived IL-4 and IL-13 had the ability to cause CD23 expression on B cells. PMA/Iono also up-regulated CD40L expression and induced a very low level expression of FasL. KU812 cells that had been activated by PMA/Iono followed by fixation could induce IgE and IgG4 synthesis in B cells in the presence of recombinant IL-4 or IL-13. This contact-dependent induction of IgE was completely abrogated by adding anti-CD40L MoAb or soluble CD40, whereas anti-FasL antibody did not significantly affect IgE production. These results indicate that activated KU812 cells produce biologically active IL-4 and IL-13, express functional CD40L, and exhibit weak induction of FasL, thereby supporting sufficient IgE production by B cells.
authors.affiliation: Clinical Research Centre for Allergy, National Sagamihara Hospital, Sagamihara City, Kanagawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagihara
authors.forename: K
authors.initials: K
authors.lastname: Kajiwara
authors.forename: Y
authors.initials: Y
authors.lastname: Basaki
authors.forename: K
authors.initials: K
authors.lastname: Ikizawa
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D001491:Basophils / Q000378:metabolism*; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand; D053222:Fas Ligand Protein; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D018793:Interleukin-13 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D019013:CD40 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D018793:Interleukin-13; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E