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

Abstract

The interleukin-2 (IL-2) receptor γ-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 γ-chain (γ(c)-chain). Transfection experiments have shown that the γ(c)-chain participates in signal transduction by IL-2, IL-4 and IL-7, but a functional role for the γ(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 γ(c)-chain gene disruption model to examine the role of the γ(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 γ(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 γ(c)-chain in receptors for IL-4 and IL-13, and the nature of the immune defect in X-SCID.