title: IL-3 and granulocyte-macrophage colony-stimulating factor strongly induce Ig secretion by sort-purified murine B cell activated through the membrane Ig, but not the CD40, signaling pathway.
abstract: Sort-purified resting murine B cells proliferate in response to dextran-conjugated anti-IgD Abs (alpha delta-dex) but fail to secrete significant amounts of Ig even after the addition of IL-1 + IL-2. We show that either IL-3 or granulocyte-macrophage CSF (GM-CSF) stimulates 10- to 50-fold enhancements in IgM secretion by sort-purified B cells treated with alpha delta-dex + IL-1 + IL-2, and that the combined actions of IL-3 and GM-CSF are typically greater than additive. Both IL-3 and GM-CSF act primarily as B cell differentiation factors, although IL-3 induces a modest enhancement in cellular outgrowth. The enhancing effects of IL-3 and GM-CSF require multivalent Ag receptor cross-linkage, mediated by alpha delta-dex, as neither cytokine induces IgM secretion in the presence of unconjugated anti-IgD Abs. Although both alpha delta-dex and IL-1 + IL-2 are required for optimal IL-3- and GM-CSF-mediated IgM secretion, both IL-3 and GM-CSF stimulate a modest IgM secretory response by cells activated with alpha delta-dex alone. In this regard, supernatant from either an activated CD4+ Th1 or Th2 clone potently induces IgM secretion by alpha delta-dex + IL-1 + IL-2-activated B cells and this is due, in large part, to the presence in these supernatants of either IL-3 and/or GM-CSF. Neither IL-3 nor GM-CSF stimulates significant IgM secretion by B cells activated through the CD40 signaling pathway alone, although the combination of CD40 and membrane Ig signaling leads to a strong enhancement of the IL-3 + GM-CSF-mediated IgM synthesis above that obtained with membrane Ig signaling alone. The demonstration that IL-3 and GM-CSF act directly as differentiation factors for B cells activated through their Ag receptor establishes a novel cytokine pathway for induction of humoral immunity.
authors.affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Snapper
authors.forename: M A
authors.initials: MA
authors.lastname: Moorman
authors.forename: F R
authors.initials: FR
authors.lastname: Rosas
authors.forename: M R
authors.initials: MR
authors.lastname: Kehry
authors.forename: C R
authors.initials: CR
authors.lastname: Maliszewski
authors.forename: J J
authors.initials: JJ
authors.lastname: Mond
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens; D002469:Cell Separation; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000502:physiology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D007072:Immunoglobulin D / Q000276:immunology*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007377:Interleukin-3 / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D011961:Receptors, Fc / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D017077:Culture Media, Conditioned; D016207:Cytokines; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007377:Interleukin-3; D011961:Receptors, Fc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor