title: IL-4 induces germ-line IgE heavy chain gene transcription in human fetal pre-B cells. Evidence for differential expression of functional IL-4 and IL-13 receptors during B cell ontogeny.
abstract: The present study demonstrates that IL-4 induces germ-line IgE heavy chain (epsilon) gene transcription in human fetal splenic mononuclear cells; fetal bone marrow cells; highly purified sorted surface (s) mu+, CD10+, CD19+ immature B cells; and s mu-, cytoplasmic mu+, CD10+, CD19+ pre-B cells derived from human fetal bone marrow. Similar to observations in normal adult B cells, TGF-beta and IFN-gamma inhibited IL-4-induced germ-line epsilon RNA synthesis in fetal pre-B cells, whereas anti-CD40 mAbs and TNF-alpha had enhancing effects, suggesting that the general mechanisms regulating germ-line epsilon transcription in adult B cells and pre-B cells are similar. IL-13 also induced germ-line epsilon RNA synthesis in s mu+, CD10+, CD19+ immature B cells, but the level of transcription induced by IL-13 was significantly less than that induced by IL-4. Anti-CD40 mAbs strongly synergized with both IL-4 and IL-13 in inducing germ-line epsilon RNA synthesis by fetal immature B cells. Interestingly, IL-13 failed to induce germ-line epsilon RNA synthesis in s mu- pre-B cells even in the presence of anti-CD40 mAbs. These distinct effects of IL-4 and IL-13 suggest that functional IL-13R are expressed at a later stage of B cell ontogeny than IL-4R, and that IL-13, in contrast to IL-4, does not regulate pre-B cell differentiation. Given the fact that IL-4 production appears to be enhanced in atopic individuals, the capacity of IL-4 to induce germ-line epsilon transcription in human fetal immature B cells and pre-B cells suggests that commitment of B cell precursors to IgE-producing cells may occur during intrauterine life and may explain the increased IgE production in neonates with a family history of atopy.
authors.affiliation: DNAX Research Institute of Molecular and Cellular Biology, Human Immunology Department, Palo Alto, CA 94304, USA.
authors.forename: J
authors.initials: J
authors.lastname: Punnonen
authors.forename: B G
authors.initials: BG
authors.lastname: Cocks
authors.forename: J E
authors.initials: JE
authors.lastname: de Vries
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D005333:Fetus; D005803:Genes, Immunoglobulin; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics* / Q000276:immunology; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D013154:Spleen / Q000166:cytology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D015703:Antigens, CD; C508181:IL13RA1 protein, human; D007143:Immunoglobulin Heavy Chains; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007073:Immunoglobulin E