title: IgE class switching is critically dependent upon the nature of the B cell activator, in addition to the presence of IL-4.
abstract: Cross-linkage of membrane IgD on resting murine B cells, by anti-IgD mAb conjugated to dextran (alpha delta-dex), induces high levels of proliferation, and in the presence of IL-2 or IL-5, Ig secretion in vitro. The structural and functional similarities between alpha delta-dex and TNP-Ficoll for B cell responses led us to propose that alpha delta-dex could provide a model system for studying B cell activation induced by T cell-independent, type II Ag. In this report, we study the effects of Ig class switch and differentiation factors on Ig isotype production by murine B cells activated by alpha delta-dex, and directly compare these to responses obtained after activation by LPS. We show that an IL-4-containing CD4+ T cell supernatant (Th2 SN) stimulates large increases in IgG1 and IgE production by LPS-activated B cells, but fails to stimulate detectable levels of IgE by alpha delta-dex-activated cells, despite inducing high levels of secreted IgM and IgG1. This is correlated with undetectable steady state levels of both germ-line and rearranged (productive) IgE-specific RNA in B cells stimulated with alpha delta-dex + Th2 SN. Alpha delta-dex is selective in its failure to costimulate IgE production in that IFN-gamma-containing T cell supernatant (Th1 SN) and transforming growth factor-beta-supplemented Th2 SN selectively stimulate a large IgG2a and IgA secretory response, respectively. Anti-IgD conjugated to Sepharose beads, in distinct contrast to dextran, costimulates a strong IgE response. These findings underscore the importance of the specific B cell activator, in addition to IL-4, in the regulation of IgE production.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
authors.forename: C M
authors.initials: CM
authors.lastname: Snapper
authors.forename: L M
authors.initials: LM
authors.lastname: Peçanha
authors.forename: A D
authors.initials: AD
authors.lastname: Levine
authors.forename: J J
authors.initials: JJ
authors.lastname: Mond
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D003911:Dextrans / Q000494:pharmacology; D005260:Female; D007072:Immunoglobulin D / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D011961:Receptors, Fc / Q000502:physiology; D017452:Receptors, IgG; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000943:Antigens, Differentiation; D003911:Dextrans; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D008070:Lipopolysaccharides; D011961:Receptors, Fc; D017452:Receptors, IgG; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007073:Immunoglobulin E