FUNCTION OF THE INTERLEUKIN-2 (IL-2) RECEPTOR GAMMA-CHAIN IN BIOLOGICRESPONSES OF X-LINKED SEVERE COMBINED IMMUNODEFICIENT B-CELLS TO IL-2, IL-4, IL-13, AND IL-15

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 recentl y been renamed the common gamma-chain gamma(c)-chain). Transfection ex periments have shown that the gamma(c)-chain participates in signal tr ansduction 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 the se cytokines has not been established. In this study, we have used X-l inked severe combined immunodeficiency (X-SCID) as a naturally occurri ng gamma(c)-chain gene disruption model to examine the role of the gam ma(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 chara cterized 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 I L-13 in assays for B cell activation, proliferation, and IgE secretion . This finding raises important questions about the function of the ga mma(c)-chain in receptors for IL-4 and IL-13, and the nature of the im mune defect in X-SCID. (C) 1995 by The American Society of Hematology.