title: Role of JAK3 in CD40-mediated signaling.
abstract: CD40 is a member of the tumor necrosis factor receptor family and plays an important role in B-cell survival, growth, differentiation, and isotype switching. Recently, CD40 has been shown to associate with JAK3, a member of the family of Janus Kinases, which are nonreceptor protein kinases involved in intracellular signaling mediated by cytokines and growth factors. To investigate the role of JAK3 in CD40-mediated signaling, we studied the effect of CD40 stimulation on B-cell proliferation, IgE isotype switching, and upregulation of surface expression of CD23, ICAM-1, CD80, and LT-alpha in JAK3-deficient patients. Our studies show that stimulation of B cells with monoclonal antibody to CD40 in the presence of interleukin-4 (IL-4) or IL-13 resulted in similar responses in JAK3-deficient patients and normal controls. This suggests that JAK3 is not essential for CD40-mediated B-cell proliferation, isotype switching, and upregulation of CD23, ICAM-1, CD80, and LT-alpha surface expression.
authors.affiliation: Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: H H
authors.initials: HH
authors.lastname: Jabara
authors.forename: R H
authors.initials: RH
authors.lastname: Buckley
authors.forename: J L
authors.initials: JL
authors.lastname: Roberts
authors.forename: G
authors.initials: G
authors.lastname: Lefranc
authors.forename: J
authors.initials: J
authors.lastname: Loiselet
authors.forename: G
authors.initials: G
authors.lastname: Khalil
authors.forename: R S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D016026:Bone Marrow Transplantation; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000954:Antigens, Surface; D019013:CD40 Antigens; D007132:Immunoglobulin Isotypes; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D015847:Interleukin-4; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3