title: Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM.
abstract: The ligand for CD40 (CD40L) is a membrane protein on activated T cells that induces B cell proliferation and differentiation. Several mutations of the CD40L gene were reported responsible for defective class switching of B cells in an X-linked immunodeficiency with hyper IgM (X-HIM). We studied four affected males from three families and found three independent mutations including new mutations of CD40L gene. In every X-HIM patient tested, however, anti-CD40 plus IL-10 did not induce class switching from IgM to IgG or IgA, even in the presence of Staphylococcus aureus Cowan I strain (SAC). CD4+ T cell clones, expressing CD40L on their surface, also did not rescue IgG or IgA induction by X-HIM peripheral blood B cells in vitro. But signaling through CD40 induced both B cell proliferation and IgE secretion when IL-4 was added to the culture. Taken together, these results show that in vitro signaling through CD40 rescues IgE but not IgG or IgA secretion by peripheral blood X-HIM B cells and suggest that in vivo CD40 and CD40L interaction might be necessary for IgG and IgA differentiation in X-HIM.
authors.affiliation: Department of Clinical Investigation, Osaka Minami National Hospital, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Saiki
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Uda
authors.forename: A
authors.initials: A
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Katada
authors.forename: M
authors.initials: M
authors.lastname: Izeki
authors.forename: M
authors.initials: M
authors.lastname: Iwata
authors.forename: H
authors.initials: H
authors.lastname: Nunoi
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology*; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D014960:X Chromosome
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D007375:Interleukin-1; D011994:Recombinant Proteins; D015847:Interleukin-4; D007073:Immunoglobulin E