title: Inhibition of interleukin 4-promoted CD23 production in human B lymphocytes by transforming growth factor-beta, interferons or anti-CD19 antibody is overriden on engaging CD40.
abstract: Interleukin 4 (IL 4) is an essential component in the sequence of events directing IgE synthesis in uncommitted B lymphocytes. An early consequence of IL 4's interaction with the B cell is the induction of CD23, a low-affinity receptor for IgE (Fc epsilon RII). The present study was designed to explore the detailed regulation of this event. First, we report that transforming growth factor-beta (TGF-beta) is a potent inhibitor of IL 4-promoted CD23 production in human B lymphocytes. The level of inhibition achieved with TGF-beta was greater than that obtained with interferons, or with a monoclonal antibody (mAb) to CD19. Next, we identified three signals, each of which was capable of selectively counteracting the inhibitors of IL 4-promoted CD23 production: (a) the engagement of surface CD40 antigen with mAb was found to override the influence of all the inhibitors of CD23 expression; (b) mAb to surface IgM overcame the inhibitory actions of TGF-beta and interferons but not that of CD19 ligation; (c) ligation of surface CD72 counteracted the inhibition mediated by TGF-beta but not that generated by interferons or anti-CD19 antibody. Inhibition of the IL 4 signal appeared to be selective for the pathway leading to CD23 induction: none of the inhibitors profoundly altered IL 4's ability to enhance surface IgM expression. The study has ramifications for the understanding of events leading to the promotion of IgE synthesis and consolidates the notion of a central role for CD40 in B cell regulation.
authors.affiliation: Department of Immunology, Medical School, Birmingham, Great Britain.
authors.forename: J
authors.initials: J
authors.lastname: Gordon
authors.forename: A
authors.initials: A
authors.lastname: Katira
authors.forename: A J
authors.initials: AJ
authors.lastname: Strain
authors.forename: S
authors.initials: S
authors.lastname: Gillis
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis* / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens; D004357:Drug Synergism; D006801:Humans; D007372:Interferons / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D011961:Receptors, Fc / Q000096:biosynthesis*; D017455:Receptors, IgE; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; C064228:CD72 protein, human; D011961:Receptors, Fc; D017455:Receptors, IgE; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007372:Interferons