Signaling through CD40 rescues IgE but not IgG or IgA secretion in X-linked immunodeficiency with hyper-IgM

• Published in: The Journal of clinical investigation 1995-02, Vol.95 (2), p.510-514
• Main Authors: Saiki, O, Tanaka, T, Wada, Y, Uda, H, Inoue, A, Katada, Y, Izeki, M, Iwata, M, Nunoi, H, Matsuda, I
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Antigens, CD - physiology; Antigens, Differentiation, B-Lymphocyte - physiology; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Base Sequence; CD4-Positive T-Lymphocytes - immunology; CD40 Antigens; Cells, Cultured; Child; Child, Preschool; Female; Humans; Immunoglobulin A - biosynthesis; Immunoglobulin E - biosynthesis; Immunoglobulin G - biosynthesis; Immunoglobulin M - biosynthesis; Immunoglobulin M - genetics; Immunoglobulins - biosynthesis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Interleukin-1 - pharmacology; Interleukin-4 - pharmacology; Lymphocyte Activation; Male; Molecular Sequence Data; Recombinant Proteins - pharmacology; Reference Values; Signal Transduction; T-Lymphocytes - immunology; X Chromosome
• ISSN: 0021-9738
• DOI: 10.1172/JCI117692

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.