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.
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.
Matthews
D J
DJ
Cellular Immunology Unit, Institute of Child Health, London, UK.
Clark
P A
PA
Herbert
J
J
Morgan
G
G
Armitage
R J
RJ
Kinnon
C
C
Minty
A
A
Grabstein
K H
KH
Caput
D
D
Ferrara
P
P
D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division; D008040:Genetic Linkage; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism; D007223:Infant; D018793:Interleukin-13 / Q000494:pharmacology; D019409:Interleukin-15; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000502:physiology*; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D013329:Structure-Activity Relationship; D014960:X Chromosome
D018793:Interleukin-13; D019409:Interleukin-15; D007376:Interleukin-2; D007378:Interleukins; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E