Synthesis of IL-13 by human B lymphocytes: Regulation and role in IgE production

• Published in: Journal of allergy and clinical immunology Vol. 114; no. 3; pp. 657 - 663
• Main Authors: Hajoui, Oumnia, Janani, Ramesh, Tulic, Meri, Joubert, Philippe, Ronis, Tova, Hamid, Qutayba, Zheng, Huaien, Mazer, Bruce D.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-09-2004; Elsevier; Elsevier Limited
• Subjects: allergy; B lymphocytes; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Biological and medical sciences; Biopsy; CD40 Antigens - immunology; Cells, Cultured; Child; Child, Preschool; cytokines; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Genes; Humans; Hypersensitivity, Immediate - immunology; IgE; IL-13; Immune system; Immunoglobulin E - metabolism; Immunoglobulins; Immunopathology; Interleukin-13 - biosynthesis; Interleukin-4 - immunology; Kinases; Lymphocyte Activation; Lymphocytes; Medical sciences; Nose - immunology; Palatine Tonsil - cytology; Palatine Tonsil - immunology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Ontario Canada; allergy; cytokines; αCD40; IL-13; B lymphocytes; IgE; Human; Allergy; Immunopathology; Regulation(control); Immunology; Cytokine; Interleukin 13; B-Lymphocyte
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2004.05.034

Our laboratory has demonstrated previously that human tonsillar B lymphocytes express IL-13 mRNA
We sought to investigate IL-13 production by human B cells and the association between B cell–derived IL-13 and IgE secretion.
Human B lymphocytes were isolated from tonsils and purified by means of rosetting with sheep RBCs or positive or negative selection with magnetic beads. They were stimulated with anti-CD40 antibodies with or without recombinant IL-4. Total mRNA was extracted, and IL-13 mRNA was measured by means of standard RT-PCR or by means of real-time PCR with commercially available primers. B cells were cultured with or without IL-13 neutralizing antibodies, and Cε transcripts and supernatant IgE levels were measured.
IL-13 mRNA was detected in human B lymphocytes stimulated with anti-CD40 antibodies and IL-4 or IL-2 but not in unstimulated B cells. Real-time PCR demonstrated a 10- to 15-fold increase in IL-13 mRNA, maximizing at 36 hours. IL-13 protein was detected from B lymphocytes on day 3 and accumulated through day 7. The synthesis of IL-13 required both CD40 and IL-4 stimulation. The presence of IL-13 was confirmed by means of intracellular staining of cultured B lymphocytes and antigen-stimulated nasal biopsy specimens from atopic individuals. Addition of IL-13 neutralizing antibodies to purified B-cell cultures inhibited IgE production by up to 80% and diminished IgE (Cε) transcripts by 50%.
Human B lymphocytes express IL-13 mRNA after ligation of CD40 and the addition of cytokines. Human B lymphocytes produce significant IL-13, and neutralization of IL-13 impairs IgE synthesis. IL-13 might be an important autocrine growth factor for IgE-producing B lymphocytes.