Function of the interleukin-2 (IL-2) receptor gamma-chain in biologic responses of X-linked severe combined immunodeficient B cells to IL-2, IL-4, IL-13, and IL-15

• Published in: Blood 1995-01, Vol.85 (1), p.38-42
• Main Authors: Matthews, D J, Clark, P A, Herbert, J, Morgan, G, Armitage, R J, Kinnon, C, Minty, A, Grabstein, K H, Caput, D, Ferrara, P
• Format: Article
• Language: English
• Subjects: B-Lymphocytes - immunology; Cell Division; Genetic Linkage; Humans; Immunoglobulin E - metabolism; Infant; Interleukin-13 - pharmacology; Interleukin-15; Interleukin-2 - pharmacology; Interleukin-4 - pharmacology; Interleukins - pharmacology; Lymphocyte Activation; Male; Mutation; Polymerase Chain Reaction; Receptors, Interleukin-2 - chemistry; Receptors, Interleukin-2 - physiology; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Structure-Activity Relationship; X Chromosome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v85.1.38.bloodjournal85138

The interleukin-2 (IL-2) receptor gamma-chain is a common component of several members of the cytokine receptor superfamily including those for IL-2, IL-4, IL-7, IL-9, IL-15, and possibly IL-13, and has recently been renamed the common gamma-chain (gamma c-chain). Transfection experiments have shown that the gamma c-chain participates in signal transduction by IL-2, IL-4 and IL-7, but a functional role for the gamma c-chain in biological responses by normal T cells and B cells to these cytokines has not been established. In this study, we have used X-linked severe combined immunodeficiency (X-SCID) as a naturally occurring gamma c-chain gene disruption model to examine the role of the gamma c-chain in human B-cell responses to IL-2, IL-4, IL-13, and IL-15. Our experiments show that B cells from two X-SCID patients with characterized gamma c-chain gene mutations do not respond to IL-2 or IL-15, but respond as well or better than normal B cells to both IL-4 and IL-13 in assays for B-cell activation, proliferation, and IgE secretion. This finding raises important questions about the function of the gamma c-chain in receptors for IL-4 and IL-13, and the nature of the immune defect in X-SCID.